Abstract
Introduction
Multiple sclerosis (MS) is a severe inflammatory neuroimmune degenerative condition affecting more than 2 million individuals worldwide. The purpose of this study was to assess the prevalence of acute periapical abscesses in patients with MS and to evaluate whether acute periapical abscesses (PAs) are more likely to affect patients who were previously infected by Epstein-Barr virus (EBV).
Methods
Integrated data of hospital patients were used. Data from the corresponding diagnosis codes for MS and acute PA were retrieved by querying the appropriate International Classification of Diseases, Tenth Revision codes in the database.
Results
Of the total hospital patient population, 0.18% were diagnosed with a history of MS. Females were more affected than males 3.25-fold. Whites were more affected than African Americans 6-fold. Whites were more affected than African Americans combined with other ethnicities 3.6-fold. The odds ratio (OR) for acute PAs in patients with a history of MS was 2.2 (P < .0001). After adjustment for diabetes mellitus comorbidity, the OR for acute PAs in patients with a history of MS was 2.6. After adjustment for cardiovascular disease comorbidity, the OR for acute PAs in patients with a history of MS was 1.27. Of the patients who presented with PAs, 0.2% were diagnosed with a history of EBV infection. The OR was 3.98, and the difference in prevalence was statistically significant (P < .0001).
Conclusions
Under the conditions of this cross-sectional study, it appears that the prevalence of acute PAs is higher in patients with MS and that EBV may play a role.
Key Words
Significance
Oral health care providers should be aware of the possible higher prevalence of acute periapical abscesses in patients with MS and a history of EBV infection.
Multiple sclerosis (MS) is a severe and debilitating disease affecting more than 2 million individuals worldwide
1
,2
. This inflammatory neuroimmune degenerative condition results from a generalized destruction of the myeline sheet of affected nerves in the central nervous system. Thus far, 3 MS distinct conditions have been identified: - 1.MS,
- 2.myelin oligodendrocyte glycoprotein antibody-associated disease, and
- 3.aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder3.
MS appears most often between the ages of 20 and 40 years
4
, generally peaking at around age 305
. It has also been reported to affect younger individuals (younger than 18 years); however, it is rare3
,6
. MS is significantly more prevalent in women than in men1
,7
. Symptoms of MS can include extreme fatigue, muscular debility, generalized pain, motor disfunction, vision and speech impairment, respiratory disorder, and amnesia, among others8
,9
.The etiology of MS is not completely understood. Genetic, epigenetic, and environmental factors have been proposed as possible causes
10
. Patients with MS suffer from low bone mineral density and increased bony fractures. Osteoporosis is a major cause of morbidity and mortality and is more common in individuals with MS than in the general population11
.It has been suggested that patients with MS exhibit a higher tendency to be affected by certain orodental diseases
1
,12
, 13
, 14
, 15
. McGrother et al12
reported a statistically significant excess of dental caries among patients with MS compared with controls. Sheu and Lin13
found an association between MS and chronic periodontitis, mainly in women. Manchery et al1
performed a systematic review of the literature and found suggestive evidence that individuals with MS may be at higher risk for periodontal disease. Another review of randomized controlled trials, cross-sectional studies, and cohort studies found that patients with MS were at higher risk for periodontal disease and poorer oral hygiene15
.Several studies strongly suggest that Epstein-Barr virus (EBV), a member of the herpesvirus family that is a common habitant of the oral cavity, plays a role in the evolution of MS
16
,17
. A recent longitudinal analysis of more than 10 million young adults found that the risk of MS increased 32-fold after infection with EBV and was not increased after infection with other viruses18
.EBV is a human virus that infects more than 90% of the world population during their lifetime
19
. After an acute outbreak, it persists in the body of the affected individual for the remainder of his or her life20
. EBV has been associated with a variety of orodental pathoses such as oral malignancy21
, Candida albicans coinfection22
, periodontal disease23
, peri-implantitis24
, and pulpal and periapical disease25
, 26
, 27
, 28
, 29
, 30
, 31
. The aims of this cross-sectional study were to assess the prevalence of acute periapical abscesses (PAs) in patients with MS and to evaluate whether acute PAs are more likely to affect patients who were previously infected by EBV.Materials and Methods
The University of Florida (UF) Integrated Data i2b2, provided by the UF Health Office of the Chief Data Officer for the period of June 2011 to January 2022, was used. The study was in compliance with the UF Institutional Review Board (IRB) and privacy rules for research on IRB-approved deidentified data sets. The study was exempted by the UF Health Center IRB because it did not include personal health information.
Data aggregate from inpatients and outpatients visiting the UF Health Center were recorded using the electronic patient record Epic system (Verona, WI; epic.com). Epic is the preferred electronic medical record system used by more than 250 health care organizations nationwide. More than 50% of the US population have their medical records in an Epic system.
The different diagnoses were coded using the International Classification of Diseases, Tenth Revision (ICD-10) international coding system. The patient population analyzed was mixed, presenting with different disease conditions including acute PAs without sinus. Individual data were not analyzed; however, all cases were diagnosed by 3 calibrated experienced dentists in a hospital setting for patients admitted to urgent care with symptoms of acute PAs. The calibrated dentists followed a strict diagnosis protocol of the emergency clinic.
A diagnosis was made based on clinical examination and imaging data confirming the diagnoses of acute PAs without a sinus tract. The inclusion criteria encompassed all patients with the corresponding diagnostic code for acute PAs without sinus (ICD-10 code K04.7) and MS (ICD-10 code G35). There were no exclusion criteria because all codes were computerized, and specific diagnoses of acute PAs in the total hospital patient population were searched using the appropriate ICD-10 code. A history of MS was retrieved by searching the appropriate query in the database. A diagnosis of MS was made by the patient's physician.
Patients with an ICD-10 diagnosis code of acute PAs were recorded, and the prevalence of acute PAs in patients with MS was compared with the prevalence in the total hospital patient population. In addition, an adjustment for diabetes mellitus (DM) and cardiovascular disease (CV) comorbidities was performed by querying the corresponding diagnosis codes (ICD-10 codes E08–E013 and ICD-10 codes I00–I99, respectively).
Logistic regression was conducted using the aggregated counts as weight in the model. Limited by i2b2 data, adjustment for DM and CV comorbidities was done for 1 covariate at a time. The SAS 9.4 (SAS Institute, Cary, NC) Logistic procedure was used to perform the statistical analysis.
Additionally, the odds ratio (OR) for the prevalence of acute PAs and its association with a history of EBV infection (ICD-10 code B27.9) in the hospital patient population was calculated and analyzed.
Results
The demographics of the hospital patient population studied is summarized in Table 1. The total hospital patient population studied was 1,314,924; 46.2% were males, and 53.8% were females (Table 1). Of the total hospital patient population, 0.18% were diagnosed with a history of MS. Females were more affected than males 3.25-fold. Whites were more affected than African Americans 6-fold. Whites were more affected than African Americans combined with other ethnicities 3.6-fold. Patients older than 18 years were affected almost exclusively. They were more affected than patients younger than 18 years more than 266-fold (Table 1).
Table 1Demographics of the Hospital Patient Population Studied
| MS (n = 2,410), n (%) | PAs (n = 7,762), n (%) | MS + PAs (n = 28), n (%) | Total patients (N = 1,314,924), n (%) | |
|---|---|---|---|---|
| Males | 566 (23.5) | 3424 (44.1) | 12 (42.9) | 607,104 (46.2) |
| Females | 1844 (76.5) | 4338 (55.9) | 16 (57.1) | 707,820 (53.8) |
| Whites | 1890 (78.4) | 4395 (56.6) | 19 (67.9) | 623,740 (47.4) |
| African Americans | 311 (12.9) | 2371 (30.6) | 9 (32.1) | 134,329 (10.2) |
| Other ethnicities | 209 (8.7) | 996 (12.8) | 0 (0) | 556,855 (42.4) |
| >18 y | 2401 (99.6) | 6749 (86.95) | 28 (100) | 1,129,992 (85.9) |
| <18 y | 9 (0.4) | 1013 (13.05) | 0 (0) | 184,932 (14.1) |
MS, multiple Sclerosis; Pas, periapical abscesses.
Of the total hospital patient population, 7762 patients (0.59%) were associated with acute PAs (Table 1). Females were more affected than males, and whites were more affected proportionally than African Americans (Table 1).
The OR for acute PAs in patients with a history of MS was 2.2, and the difference in prevalence compared with the total hospital patient population was statistically significant (P < .0001) (Table 2). After adjustment for DM comorbidity, the OR for acute PAs in patients with a history of MS was 2.6 (Table 3). After adjustment for CV comorbidity, the OR for PAs in patients with a history of MS was 1.27 (Table 4).
Table 2Logistic Regression Result for Multiple Sclerosis (MS) and Periapical Abscesses (PAs)
| Response: MS | Coefficient (OR) | 2.50% | 97.50% | P value | |
|---|---|---|---|---|---|
| Intercept | 1.40E-03 | 1.34E-03 | 1.46E-03 | .0000 | |
| PAs | Yes vs no | 2.2 | 1.44 | 3.23 | .0001 |
OR, odds ratio.
Table 3Logistic Regression Result for Multiple Sclerosis (MS) and Periapical Abscesses (PAs) Adjusted for Diabetes Mellitus (DM) Comorbidity
| Response: MS | Coefficient (OR) | 2.50% | 97.50% | P value | |
|---|---|---|---|---|---|
| Intercept | 1.27E-03 | 1.22E-03 | 1.33E-03 | .0000 | |
| PAs | Yes vs no | 2.6 | 1.38 | 2.93 | .0002 |
| DM | Yes vs no | 3.17 | 2.81 | 3.55 | .0000 |
OR, odds ratio.
Table 4Logistic Regression Result for Multiple Sclerosis (MS) and Periapical Abscesses (PAs) Adjusted for Cardiovascular (CV) Diseases Comorbidity
| Response: MS | Coefficient (OR) | 2.50% | 97.50% | P value | |
|---|---|---|---|---|---|
| Intercept | 8.82E-04 | 8.34E-04 | 9.32E-04 | <.0001 | |
| PAs | Yes vs no | 1.27 | 0.83 | 1.86 | .2438 |
| CV | Yes vs no | 4.62 | 4.27 | 5.01 | <.0001 |
OR, odds ratio.
Of the total hospital patient population, 0.05% were diagnosed with a history of EBV infection (Table 5). Of the patients who presented with acute PAs, 0.2% were diagnosed with a history of EBV infection (Table 5). The OR was 3.98, and the difference in prevalence was statistically significant (P < .0001) (Table 5).
Table 5Prevalence of Acute Periapical Abscesses (PAs) in Patients with a History of Epstein-Barr Virus (EBV) Infection
| PAs | Total patients | |
|---|---|---|
| EBV, n (%) | 15 (0.2) | 639 (0.05) |
| Hospital | 7762 | 1,314,924 |
| OR | 3.98 | |
| 95% CI | 2.3821–6.6386 | |
| P value | <.0001 |
CI, confidence interval; OR, odds ratio.
Discussion
The results of this hospital-based study show that overall the OR for the prevalence of acute PAs is significantly higher in patients with MS than in patients without this condition. Although the prevalence of acute PAs in the general hospital population was relatively low, the prevalence of acute PAs in patients with MS was more than 2-fold higher than in non-MS patients.
It has been reported that comorbidities such as DM and CV may be associated with an increased prevalence for periapical disease
32
, 33
, 34
. The results of our study show that even after adjusting for DM comorbidity, the OR for the prevalence of acute PAs in patients with MS was still higher than that of the general hospital population. However, the OR was significantly reduced and became nonsignificant after adjusting for CV diseases, suggesting that this comorbidity plays an important role in the MS PA association.Patients with MS often suffer from changes in bone metabolism that can lead to osteoporosis and osteopenia
35
, 36
, 37
. Osteoporosis may affect up to 30% of patients with MS, and osteopenia may affect more than 70% of such patients. A cross-sectional hospital-based study reported that the prevalence of acute PAs was significantly higher in patients with osteoporosis than in patients without osteoporosis38
. Patients with osteoporosis are more prone to pathologic changes in the jaw bones39
. Therefore, it is plausible that osteoporosis resulting from MS can further expose affected MS patients to the risk of poorer bone quality, bone resorption, and bone infections.Although multiple factors may be involved in affecting bone metabolism in patients with MS, it has been suggested that the induction of the tumor necrosis factor–related apoptosis-inducing ligand and interferon-beta may influence osteoclastogenesis in these patients
40
.A quintessential longitudinal analysis has strongly implicated MS, a chronic neurodegenerative disease, with previous infection with EBV. The frequency of MS was significantly higher in patients with a history of EBV infection
18
. The skeletal and bony effects of EBV have been recognized and documented22
, 23
, 24
, 25
. Our finding showing an increased prevalence of PAs in EBV-infected patients may be significant and confirmatory to the EBV-MS association.Studies showed an association between EBV infection and symptomatic apical periodontitis
41
, 42
, 43
. It was suggested that most teeth with necrotic pulp and periapical lesions harbored herpesviruses, including EBV, in the periapical tissues41
. Sabeti et al42
, using reverse-transcription polymerase chain reaction, found evidence of EBV in periapical lesions and suggested that EBV activation participated in the pathogenesis of symptomatic periapical lesions. Furthermore, it has been theorized that EBV infection was capable of damaging tissue defenses in situ, thereby permitting overgrowth of pathogenic microorganisms and causing clinically acute symptomatic periapical lesions42
,43
.Several limiting factors should be taken into consideration. First, this is a retrospective cross-sectional study of charts and as such cannot necessarily indicate causality. Second, the study design does not allow for simultaneous multivariant analysis of all possible covariables. Third, socioeconomic reasons may influence the decision of certain patients when seeking a location for their medical and dental care. Therefore, the prevalence of acute PAs in this study may also reflect social-economic disparities. Nonetheless, the results of this study suggest an association between MS and acute PAs and that EBV may play a role.
Acknowledgments
The authors deny any conflicts of interest related to this study.
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Article info
Publication history
Published online: December 13, 2022
Identification
Copyright
© 2022 American Association of Endodontists.
