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Oral health in Behçet’s disease and its association with disease severity: a case-control study
Abstract
Background
Behçet’s disease is a chronic autoimmune disorder that affects various organs, including oral aphthae, genital ulceration, cutaneous manifestation, ocular involvement, and positive pathergy test according to the International Study Group for Behçet’s Disease criteria. This study aimed to investigate the oral health condition of patients with Behçet’s disease and to assess how it correlates with the patient’s gender, clinical symptoms, and severity of the disease.
Methods
A total of 92 participants, including 42 patients with Behçet’s disease and 50 healthy controls, were enrolled in this case-control study. The periodontal indices were measured and compared between the two groups. Logistic regression analysis was used to identify potential risk factors for disease severity. The P value must be ( P <0.05) to be considered as significant.
Results
This study assessed the periodontal health of patients with Behçet’s disease and found that they had significantly higher plaque, gingival, bleeding, and probing depth scores compared to healthy controls ( P <0.05). Logistic regression analysis revealed that plaque accumulation was a significant risk factor for higher severity scores in Behçet’s disease. Gender-specific approaches may be necessary in the management and treatment of periodontal disease in Behçet’s disease patients.
Conclusions
The findings of this study suggest that patients with Behçet’s disease are at increased risk for periodontal disease and its associated symptoms. Specifically, plaque accumulation is a significant risk factor for more severe periodontal health issues in these patients. Therefore, it is important for clinicians to be aware of this increased risk and to develop tailored treatment plans that address both the underlying Behçet’s disease and the associated periodontal disease.
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Behçet’s disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-β) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1β, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1β (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1β, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-β and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.
Background
Behçet’s disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions.
Methods
We conducted a cross-sectional study using data from the RISE registry (2014–2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas.
Results
One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran.
Conclusions
Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management.
Behçet’s disease (BD) is a multisystem autoinflammatory condition characterized by mucosal ulceration, breakdown of immune privilege sites and vasculitis. A genetic basis for BD has been described in genome-wide and validation studies. Similarly, dysbiosis of oral and gut microbiomes have been associated with BD. This review will describe links between genetic polymorphisms in genes encoding molecules involved in gut biology and changes seen in microbiome studies. A potential decrease in bacterial species producing short chain fatty acids linked to mutations in genes involved in their production suggests a potential therapy for BD.
Behçet's disease (BD) is a chronic multi-systemic inflammatory disorder characterised by oro-genital ulcers, cutaneous manifestations, ocular, vascular, neurologic and gastrointestinal involvement. Complex interactions operating on the genetic background e.g.(HLA51), of infectious and other environmental agents, together with immune dysregulation impacts on the pathogenesis of BD. This suggests that the environmental factors triggering immune responses may activate clinical manifestations in genetically susceptible individuals. Since oral health forms the basis of all general health both dental and systemic, it is an important component of both Dentistry and Medicine. Oral ulcers are the most common clinical manifestation of oral mucosal health. Changes in the oral environment consequently acts as an infective and immune trigger. In this review, complex interactions between the oral ulcers, the oral microbiome and immune responses together with the course of oral and systemic disease manifestations in BD are discussed in the context of the aetiologic role of oral health.
Behçet's disease (BD) is a chronic, relapsing inflammatory, multisystem disease of unknown etiology. The disease has a wide clinical spectrum of mucocutaneous lesions and ocular, vascular, articular, neurologic, gastrointestinal and cardiac involvement. Although the number of effective drugs used in the disease's treatment has increased in recent years, BD is still associated with severe morbidity because of mainly mucocutaneous, articular and ocular symptoms and an increased mortality because of large vessel, neurological, gastrointestinal and cardiac involvement. Many factors are associated with a more serious course, such as male gender and a younger age of onset. While the severity of the disease is more pronounced in the first years of the disease, it decreases in most patients after the age of forties. The primary goal of treatment should be the prevention of irreversible organ damage. Therefore, early diagnosis and appropriate treatment and close follow-up are mandatory to reduce the morbidity and mortality of the disease. Treatment varies depending on the organ involved and the severity of the involvement. For all these reasons, the treatment should be personalized and arranged with a multidisciplinary approach according to the organs involved. Treatment is mainly based on suppression of the inflammatory attacks of the disease using local and systemic immunomodulatory and immunosuppressive drugs. In this review, based on the mainly controlled studies and personal experience in clinical practice and basic research in this field, we propose a stepwise, symptom-based, algorithmic approach for the management of BD with a holistic perspective.
The triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.
Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B*51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B*51, may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B*51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis.
Behcet's disease (BD) is a chronic systemic inflammatory vasculitis of unknown etiology characterized by recurrent episodes of oral aphthous ulcers, genital ulcers, skin lesions, ocular lesions, and other manifestations. Although the pathogenesis of BD is unclear, some studies have shown that immunological aberrations play an important role in the development and progression of BD. Infection-related trigger factors, including antigens and autoantigens, are believed to mediate the development of BD in patients with a genetic predisposition and subsequently activate the innate and adaptive immune systems, resulting in the production of numerous cytokines and chemokines to combat the infection-related factors. The study of the immunological mechanism of BD paves the way for the development of innovative therapies. Recently, novel biotherapy approaches, including interferon-α (IFN-α), tumor necrosis factor-α (TNF-α) antagonists, and other agents that target interleukins and their receptors, have shown promising results in the treatment of patients with refractory BD and have improved the prognosis of BD. In this review, we provide the current concepts of BD immunopathogenesis.
Behçet’s disease is a systemic disorder of unknown etiology. It involves multiple organ systems and is characterized by recurring episodes of oral ulcers as well as ocular, genital, and skin lesions. Oral ulcers can affect tooth brushing and impair proper oral hygiene. As a result, a dental biofilm accumulates, and the condition of the teeth and periodontal tissue deteriorates. The aim of this case report is to highlight the efficacy of periodontal treatment for patients with Behçet’s disease. A 51-year-old man with Behçet’s disease presented with generalized severe periodontitis. After basic treatment of the periodontal tissues, periodontal surgery was performed at several sites with bony defects. However, the patient developed severe stomatitis in the oral mucosa and gingiva after periodontal surgery. Administration of the antimicrobial agent cefdinir had little effect on recovery; however, subsequent administration of sitafloxacin resulted in significant improvement of the stomatitis. This case demonstrates that periodontal therapy is very useful for alleviating the oral signs and symptoms of Behçet’s disease. Systemic antibiotic treatment with sitafloxacin (but not cefdinir) and mechanical debridement were effective in preventing the recurrence of aphthous ulcer outbreaks after periodontal surgery.
We aimed to evaluate the relationship of individual periodontal parameters with the severity of Behçet’s disease (BD) and attempt to find the correlation between chronic periodontitis and BD. In this study, 74 registered subjects attending Behçet’s clinic with BD symptoms were recruited. The diagnosis was based on the criteria presented by the international study group for BD (ISG) and the total clinical severity score was determined for each patient. All individuals underwent clinical examination to assess oral and periodontal status and presence of oral ulcers. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and also hygiene index (HI) and decayed, missing, and filled (DMF) teeth were noted and analyzed to assess the correlation with severity of BD. There was no significant correlation between DMF and severity of BD. The strong association was found between periodontal parameters (BOP, PD, and CAL) and the severity of BD (
P
<
0.001
). It seems that relation of BD to oral health is higher up in severe forms of BD and periodontal diseases. Clinical association between the diseases might be due to a common underlying etiopathogenesis of periodontitis and BD.
Behçet's disease (BD) is a multi-systemic vascular disorder characterized by oral and genital ulcers, cutaneous, ocular, arthritic, vascular, central nervous system and gastrointestinal involvement. It usually affects young adults and the etiopathogenesis is unknown. A 21-year-old girl, Caucasian, with diagnostic BD, presented with rheumatoid arthritis, genital lesions and multiple recurrent ulcers inside the mouth, with an erythematous halo, covered by yellowish exudates exacerbated during menstrual periods, and in situations of stress and anxiety. The application of low power laser in ulcers was considered in order to decrease the inflammatory symptoms and pain, beyond getting the healing process accelerated. The proposed therapy was able to promote pain relief, increase local microcirculation and repair ulcerated lesions, eliminating the need for administration of systemic or topical medications, leading to improved quality of life.
Behcet's disease (BD) significantly increases morbidity and mortality. BD mainly affects young adults with a peculiar geographical distribution. It has been suggested that BD varies in its phenotypic expression in different ethnic groups.
We investigated potential ethnicity-related differences relative to phenotype and prognosis of BD patients in a French multiethnic country. We included 769 consecutive patients fulfilling the international criteria of classification for BD, in the 3 largest ethnic groups of our cohort [European (n = 369), North African (n = 350) and sub Saharan African (n = 50)]. Factors that affect prognosis were assessed by multivariate analysis.
535 (69.6%) patients were male and the median (IQR) age at diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51 allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa and Europe, respectively. Multivariate analysis showed that male gender (HR: 5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan African, North African and European BD patients, respectively (p = 0.015).
We reported ethnicity-related differences with respect to phenotype of BD. Sub Saharan Africans patients exhibited a worse prognosis.
Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects.
Behçet's disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçet's disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçet's disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçet's disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role.
Historical Background. The ISG criteria for Behcet's, created in 1990, have excellent specificity, but lack sensitivity. The International Criteria for Behcet's Disease (ICBD) was created in 2006, as replacement to ISG. The aim of this study was to compare their performance.
ISG and ICBD Criteria. For ISG oral aphthosis is mandatory. The presence of any two of the following (genital aphthosis, skin lesions, eye lesions, and positive pathergy test) will diagnose/classify the patient as BD. For ICBD, vascular lesions were added, while oral aphthosis is no more mandatory. Getting 3 or more points diagnose/classify the patient as BD (genital aphthosis 2 points, eye lesions 2 points, and the remaining each one point).
Performance and Comparison of ISG and ICBD. Their sensitivity, specificity, and accuracy (percent agreement), were tested in three independent cohort of patients from Far-East (China), Middle-East (Iran), and Europe (Germany). The sensitivity for ISG was respectively 65.4%, 78.1%, 83.7% and for ICBD 87%, 98.2%, and 96.5%. The specificity for ISG was 99.2%, 98.8%, 89.5% and for ICBD 94.1%, 95.6%, and 73.7%. The accuracy for ISG was 74.2%, 85.5%, 85.5% and for ICBD 88.9%, 97.3%, and 89.5%.
Conclusion. ICBD has better sensitivity, and accuracy than ISG.
Tacrolimus is a potent immunomodulator that is effective in the treatment of inflammatory bowel disease (IBD). However, potential toxicity and systemic effects with oral intake limit its use. Local tacrolimus treatment is effective in a subgroup of proctitis patients. This study aimed to evaluate whether colonic mucosal immune cells are susceptible to locally applied tacrolimus in vitro. Our in vivo studies aimed at evaluating whether local tacrolimus treatment in mice would bring about local immune suppression and to compare colonic and systemic tacrolimus levels after locally and systemically applied tacrolimus.
In vitro tacrolimus inhibited the activation of multiple cell types present in colonic tissue; lamina propria T cells, NKT cells, and both classical- and non- classical antigen presenting cells. However, the cytokine production of epithelial cells was not inhibited by tacrolimus at these concentrations. After rectal administration in mice, tacrolimus blood levels were comparable to those obtained by oral intake. However, rectally treated mice exhibited a 14-fold higher concentration of tacrolimus within their colonic tissue than orally treated mice. Moreover, rectally applied tacrolimus resulted in a local but not a systemic immune suppression in mice.
Tacrolimus inhibits activation of several pivotal immune cells of the intestinal mucosa. Murine studies indicate that colonic application of tacrolimus induces local rather than systemic immune suppression.
Saliva coating all oral surfaces has a buffering capacity that neutralizes bacterial and cariogenic acids. The aim of our study was to determine the surface pH in different regions of the oral cavity in healthy volunteers and in patients with diseases affecting the oral mucosa. Oral pH was measured with a flat glass electrode on the anterior third of the ventral surface of the tongue, middle hard palate, buccal mucosa and inner lips in 32 healthy volunteers, 12 patients with Behçet's disease, 23 patients with oral lichen planus, and 11 patients with burning mouth syndrome. The present study showed that there was an uneven distribution of oral surface pH. The palate had a higher pH than most other sites in all groups, and in patients with lichen planus, the palate pH was higher than that in healthy controls. Those with dentures had lower pH values in the hard palate than dentate patients. The relatively high pH in the palate region in all patient groups as well as healthy volunteers needs to be further studied to clarify its mechanisms and clinical relevance.
This study aimed to investigate the oral health of Turkish patients with Behçet's disease (BD) and whether it is associated with the disease course.
One hundred and twenty patients with BD, 35 patients with recurrent aphthous stomatitis (RAS) and 65 healthy Turkish controls (HC) were included in the study. Oral health was investigated by indices applied in a BD out-patient clinic.
The mean scores of plaque, sulcus bleeding and gingival indices, probing depth and the number of extracted teeth were observed to be higher in patients with BD and RAS compared to HC (P<0.05). In the linear regression analysis, plaque index score was associated with the presence of oral ulcers and male gender. An elevated plaque index score was observed to be a significant risk factor for increased severity score in patients with BD in the logistic regression analysis (P = 0.034).
Oral health is impaired in BD and associated with disease severity. Improvement of the oral health of BD patients may affect their disease course, leading to a better prognosis.
Introduction
Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines.
Methods
A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise.
Results
42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items.
Conclusion
We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.
Objectives:
Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS).
Methods:
DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora.
Results:
Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group.
Conclusions:
The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.
The oral mucosa is a primary barrier site and a portal for entry of microbes, food, and airborne particles into the gastrointestinal tract. Nonetheless, mucosal immunity at this barrier remains understudied compared with other anatomical barrier sites. Here, we review basic aspects of oral mucosal histology, the oral microbiome, and common and clinically significant diseases that present at oral mucosal barriers. We particularly focus on the role of interleukin-17 (IL-17)/T helper 17 (T H 17) responses in protective immunity and inflammation in the oral mucosa. IL-17/T H 17 responses are highly relevant to maintaining barrier integrity and preventing pathogenic infections by the oral commensal fungus Candida albicans . On the other hand, aberrant IL-17/T H 17 responses are implicated in driving the pathogenesis of periodontitis and consequent bone and tooth loss. We discuss distinct IL-17–secreting T cell subsets, emphasizing their regulation and function in oropharyngeal candidiasis and periodontitis.
Three recent advances in immunology, genetics, and microbiology have ushered in a new era in the continued efforts to better understand and treat oral diseases, moving ever closer to the three Ps of modern healthcare: personalized, predictive, and preventive medicine (PPPM). The discovery of now 15 subtypes of innate lymphoid cells, the refinement of DNA sequencing, and culture-independent characterization of the entire microbial community begin to reveal this complex adaptive network. All these advances warrant a systematic review as they have changed and will continue to change dental medicine. We will update dental professionals on these advances as related to oral diseases and associated pathologies in other organ systems such as premature labor, arthrosclerosis, and cancer. The five objectives are:
1.
Introduce the concept of microbiota and microbiome
2.
Explain how we study microbiota and microbiome
3.
Describe the types and functions of innate lymphoid cells
4.
Inventory the unique demands of the oral cavity
5.
Provide a heuristic model to integrate the above
6.
Conclusions and expert recommendations
Objectives
The aim of the study was to examine whether oral health as an infection focus could mediate disease course in patients with Behçet's disease (BD).
Methods
In the study, oral health of 194 BD patients was examined at baseline and follow‐up periods. The reasons for last dental visits were recorded as tooth extraction or regular control visits/planned treatments at the end of follow‐up period. The Behçet's disease severity score was calculated with higher scores indicating a more severe course. Mediation analysis was carried out to assess the effects of oral health on disease severity score at follow‐up period in the study.
Results
Dental and periodontal indices were found to be higher at follow‐up visit compared to those of baseline (p<0.05). Disease severity score was found to be higher in males (5.3±2.4) compared to females (4.4±2.5) in the whole group (p=0.005). Moreover, patients having tooth extraction at their last dental visit and patients with dental caries had a more severe disease course (5.4±2.4; 5.5±2.5) compared to others (4.2±2.3; 4.4±2.4)(p<0.0001). In multiple mediation analysis, disease severity score was a dependent variable and was directly mediated by male gender (B=‐0.8822, p=0.0145) and indirectly mediated through the presence of dental caries (B=0.9509 p=0.0110) and need of tooth extraction (B=0.8758 p=0.0128).
Conclusion
Both presence of dental caries and need of tooth extraction were observed to be effective mediators for a more severe disease course in BD. Therefore, better oral health should be aimed to eliminate microbial factors, which are a part of pathogenic processes.
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Objectives:
The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.
Methods:
A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes.
Results:
Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study.
Conclusions:
RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.
Introduction:
Behcet's Disease (BD) is classified among vasculitides. The aim of this review was to put together different known reports in order to help the reader to better understand the disease, to avoid the frequent misdiagnosis, and to decide the best treatment.
Areas covered:
a) Epidemiology: BD is rare, and is seen along the Silk Road, from 20 to 420/100,000 in Turkey and 80/100,000 in Iran, to 0.64/100,000 in the UK. b) Clinical manifestations: oral aphthosis is seen in more than 95% of patients, genital aphthosis (60-90%), skin (pseudofolliculitis/erythema nodosum, 40-90%), eyes (uveitis/retinal vasculitis, 45-90%), gastrointestinal (diarrhea/hemorrhage/perforation/pain, 4-38%), vascular (venous/arterial thrombosis, aneurysm, 2.2-50%), neurological (all kinds, especially meningo-encephalitis, 2.3-38.5%), and articular (arthralgia/arthritis/ankylosing spondylitis, 11.6-93%). c) Pathergy test is positive in some patients: 8.6% (in India) to 70.7% (in China). This data was extracted from the five nationwide surveys and the largest case series from BD conference reports and a Pubmed search. Expert commentary: Diagnosis is clinical but classification/diagnosis criteria may help. The best criteria for BD is the International Criteria for Behcet's Disease (ICBD). BD is a multisystem disease progressing by attacks and remissions. Each attack may resemble the preceding or it may be different in duration, severity, and the systems involved.
Background:
Chronic recurrent oral aphthous ulcers are the most common type of inflammatory efflorescence of the oral mucosa, with a prevalence of 2% to 10% in Caucasian populations. To treat them properly, physicians should know their clinical appearance and course, conditioning factors, underlying causes, and differential diagnosis.
Method:
This review is based on pertinent articles that were retrieved by a selective search in PubMed and in the Cochrane Central Register of Controlled Trials.
Results:
Hard, acidic, and salty foods and toothpastes containing sodium lauryl sulfate should be avoided, along with alcohol and carbonated drinks. In Germany, the only drugs that have been approved to treat oral aphthous ulcers are corticosteroids, topical antiseptic/anti-inflammatory agents such as triclosan and diclofenac, and local anesthetics such as lidocaine. Antiseptic agents and local anesthetics should be tried first; if these are ineffective, topical cortico steroids should be used. In severe cases, local measures can be combined with systemic drugs, e.g., colchicine, pentoxifylline, or prednisolone. The efficacy of systemic treatment is debated. Other immunosuppressive agents should be given systemically only for refractory or particularly severe oral aphthous ulcers due to Adamantiades-Behçet disease.
Conclusion:
The treatment of chronic recurrent oral aphthous ulcers is symptomatic, mainly with topically applied agents. It is tailored to the severity of the problem in the individual case, i.e., the frequency of ulcers, the intensity of pain, and the responsiveness of the lesions to treatment. Effective treatment relieves pain, lessens functional impairment, and lowers the frequency and severity of recurrences.
Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful for following disease activity. Components of the laboratory examination include a complete blood count with differential, a comprehensive metabolic panel, measurement of inflammatory markers and autoantibodies, and flow cytometry. This chapter discusses these components and includes a discussion about organ-specific immunologic diseases for which immunologic laboratory testing is used. Comprehensive laboratory evaluation of a suspected autoimmune illness in conjunction with a thorough clinical evaluation provides a better understanding of a patient's immunologic disease.
We report a case of Behçet's disease aggravated by gingivitis and carious teeth infected with methicillin-resistant Staphylococcus aureus. Recurrent severe ulcers in the mouth, and on the genitalia and legs were closely linked with the infection, and dramatically improved after extraction of the carious teeth and administration of systemic vancomycin hydrochloride.
Behçet's disease is a chronic, multisystem disorder. It has 3 primary components: recurrent inflammations of the eye, ulcerations of the oral mucous membranes, and ulcerations of the genitalia. Diagnosis of Behçet's disease relies mainly on history taking and clinical manifestations. This article describes the oral soft tissue and dental complications and the prosthetic problems encountered in a young patient. If dentists encounter patients with chronic ocular inflammations and recurrent oral mucous membrane ulcers, the index of suspicion should increase.
Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.
Oral tacrolimus, approved for the prophylaxis of organ rejection in liver or kidney transplants, has been reported to be effective in anecdotal cases of refractory inflammatory bowel disease.
To evaluate the usefulness of low-dose oral tacrolimus in refractory inflammatory bowel disease.
Thirty-one adult Caucasian patients with steroid-dependent (n = 15) or steroid-refractory (n = 16) inflammatory bowel disease (Crohn's disease, n = 6; ulcerative colitis, n = 23; pouchitis, n = 2) were enrolled. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in 30 patients and initially intravenously in one patient (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-6 ng/mL. The median treatment duration was 12 months (range, 1-137 months).
Twenty-eight patients (90.3%) experienced a clinical and laboratory response and 20 (64.5%) went into remission. One ulcerative colitis patient and two Crohn's disease patients did not improve. Three ulcerative colitis patients (9.7%) were colectomized at 1, 12 and 24 months after tacrolimus initiation. In 19 of 23 patients (82.6%) taking steroids, steroids were reduced or discontinued. Side-effects included a temporary rise of creatinine (n = 3, 9.7%), tremor or paraesthesias (n = 3, 9.7%), hyperkalaemia (n = 1, 3.2%), hypertension (n = 1, 3.2%) and an opportunistic infection (n = 1, 3.2%).
Oral tacrolimus is safe and effective in refractory inflammatory bowel disease.
To review the potential of periodontal infections to cause nonoral diseases. Therapeutic recommendations are provided to help patients and dental practitioners prevent systemic complications from periodontal infections.
Systemic diseases from oral bacteria are mostly caused by transient bacteraemias, which can occur spontaneously from dental foci of infection, from mastication, brushing, flossing or other daily manipulations, or from dental treatments. Examples of systemic infections that may involve oral microorganisms include infective endocarditis, aspiration pneumonia, HIV-related disseminated candidiasis and cancrum oris, septicaemia associated with cancer chemotherapy and radiotherapy, necrotising faciitis and various other life-threatening infections. Inflamed gingiva constitutes a significant reservoir for herpes viruses, which have the potential to cause serious systemic diseases in immunocompromised patients. Periodontal disease may also aggravate chronic insulin insensitivity and thus interfere with glycaemic control in diabetic patients. Controversy surrounds the involvement of periodontal infections in coronary heart disease.
Cumulative evidence suggests that periodontal disease can be an important cause of morbidity and mortality of various systemic diseases, especially in individuals exhibiting compromised host defence. Maintaining a healthy dentition and periodontium by means of daily oral hygiene practice and regular professional care is the most effective way of preventing systemic diseases from oral infections.
International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease
- Wechsler
Clinical manifestations and diagnosis of Behçet’s syndrome
- Smith
Síndrome de Behçet: revisión de la literatura y presentación de Caso Clínico. Revista Española de Cirugía
- Tarquinio Marinho