Genital and Oral Microbiome and Behçet’s Disease Activity

BackgroundThe aetiopathogeneses of Behçet’s Disease (BD) remains elusive with multifactorial genetic and epigenetic factors resulting in multisystemic disease. Oral and genital ulceration are common and influences disease outcome. We hypothesised that dysregulation of genital and oral microbial communities contributes to BD disease activity. 153 BD patients’ samples, 70 matched oral and genital (Female: Male, 58:12; mean age, 42±13.9: 39.3±10.3), 12 unmatched samples; 16s rRNA sequencing utilised and V1/V2 and V3/V4 regions analysed. BD outcomes: oral and genital ulcer severity and BD activity scores, Psychological and Social Well-being scales, Headache Impact Test-6 (HIT-6) were included. All the analyses were performed with R software. ResultsThe alpha and beta diversity had anatomical specificity, with significant differences between genital and oral samples; p values<0.05 irrespective of presence or absence of ulcers. Interestingly, in the genital area Bacteroidota were present (G_U: 29% - 10%) and (G_nU: 27% - 14%) compared to less than 1% oral area of V1/V2 and V3/V4. Proteobacteria were uniquely present with (O_U: 9%) and (O_nU: 12%) in oral, and less than 0.01% in genital area for V3/V4 region. Gender anatomical specific communities were noted: females with genital ulcers Gardnerella, Lactobacillus, Atopobium were significantly increased compared to than males, with V3/V4 analysis indicating that Lactobacillus and Gardnerella were significantly increased by 20 times in females than males (p-adj <0.05). In contrast Peptoniphilus and Corynebacterium were significantly increased in males than females. Streptococcus was significantly increased with oral ulceration, while Veillonella was significantly decreased in patients without oral ulceration. Colchicine had a significant effect on the bacterial abundance irrespective of the presence or absence of ulceration. In this cohort, the WSAS (Work and Social Adjustment Scale) values were higher in active disease. ConclusionOur results suggest that dysregulated microbial communities occur in BD. V1/V2 demonstrates that during episodes of ulceration the pathogenic bacteria genus Escherichia-Shigella appear in both oral and genital ulcers. V3/V4 outcomes show that ulceration in both regions is assigned to genus; Lachnospiraceae, Saccharimonidales, Coriobacteriales. Streptococcus is related to the presence of oral ulcers, while Veillonella is presence when patients are ulcers free may be a useful marker of disease regression.

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet’s Disease

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.

Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity

BackgroundLittle is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms.MethodsA 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p &lt; 0.05).ResultsStatistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36–48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12–24 h (lag1: r=–.322; p&lt;.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48–60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=–.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84–96 h (lag7: r=–.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=–.193; p=.042); after 84–96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect.ConclusionsThe results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.

Oral ulceration and vesiculobullous conditions in the paediatric patient

Deviations from the normal appearance of pale, pink and healthy mucosa require close monitoring or intervention and may be a sign of an underlying systemic disorder. Therefore, it is important that there is timely identification of abnormalities, appropriate management in primary care and onward referral for investigation to specialist services when required. Oral ulceration is the most common soft tissue abnormality in children, with recurrent aphthous stomatitis being the most common type of ulceration. This article discusses the various causes of oral ulceration in addition to vesiculobullous conditions, which may affect the paediatric patient. CPD/Clinical Relevance: It is important that GDPs are aware of the range of causes of ulcers and blisters presenting in children and are aware of when to refer.

Awareness Regarding Oral Aphthous Ulcers and its Risk Factors Among BDS and MBBS Students-A Cross-Sectional Survey

OBJECTIVE: The objective of this paper was to assess the awareness regarding oral aphthous ulcers and its risk factors among BDS and MBBS students in private institute of Karachi, Pakistan. METHODOLOGY: A cross-sectional survey was conducted at a private institute of Karachi Pakistan for the duration of six months. Medical and dental students of age more than 18 years of either gender were enrolled in the study using non-probability convenience sampling technique. Pre-designed proforma was used to collect data regarding demographics, history of recurrent aphthous stomatitis and knowledge of oral aphthous ulcers and its risk factors. The knowledge score of 4 out of 6 was considered as adequate knowledge. SPSS version 25 was used to analyze data. RESULTS: Of 150 participants, the mean age was reported as 22.94±1.65 years (range: 21-25 years). In those 150 participants 46 were males (30.7%) and 104 were females (69.3%). Overall mean score of knowledge was 4.35±1.29. Wherein 73% had adequate knowledge regarding oral ulceration and its risk factors. The dental students had significantly higher proportion of adequate knowledge regarding oral ulceration than medical students [p=0.024]. CONCLUSION: Overall students had good knowledge of oral ulceration and its risk factors, wherein knowledge of dental students was better than medical students. KEYWORDS: Oral ulcers; Recurrent Aphthous stomatitis; awareness, oral ulceration, risk factors, eating habits

EBV-positive mucocutaneous ulceration

Ulceration of the oral cavity is common and a frequent reason for referral to secondary and tertiary centres. Epstein–Barr virus (EBV)-related mucocutaneous ulceration, however, is a rare cause of oral ulceration that has been described only recently. Histologically these lesions resemble lymphomas; however, their management and prognosis differ significantly. We present a case of EBV-induced oral ulceration and discuss the diagnosis and management of and available literature for the condition, which was treated successfully through conservative measures alone.

Fifteen-minute consultation: oral ulceration in children

ObjectiveTo review common presentation of oral ulcers in children and discuss management of symptoms and subsequent investigation.ConclusionAlthough a common presentation in children, diagnosis can be challenging. Thorough history taking is critical towards diagnosis and supports signposting to relevant specialities. Clinicians should be able to support first-line symptomatic management of oral ulceration.

Sjögren's Syndrome in Children: About 15 Cases in Guinea Conakry

Objectives- Sjögren's syndrome is difficult to diagnose in the African context. It is rarely reported in children in Black Africa. We report a series of 15 cases of Sjögren’s syndrome in order to clarify the particularities of this condition in children.Methods- This 2-year retrospective study focused on children under 16 years of age with a male predominance who were followed for AS in the rheumatology and pediatrics departments. Patient data were collected and analyzed using STATA/SE version 11.2 software. Anonymity and respect for ethical rules were the norm. There was no link between patients and researchers.Results- The average age of the patients was 11 years with extremes of 5 to 15 years. An anamnesis revealing dry mouth was found in more than half of the cases, i.e. in 10 (66.7%) patients. The clinical examination found oral ulceration and periodontitis in equal proportions, i.e. 6 (40%). The immunological assessment and the biopsy of the accessory salivary glands were used as diagnostic evidence in the 15 patients according to the American-European criteria of 2002.Conclusion- Sjögren's syndrome is a rare entity in pediatrics. It is difficult to diagnose in pediatrics and its severity is linked to the occurrence of visceral and lymphomatous late dry syndrome. Rapid diagnosis and the use of a synthetic antimalarial drug (Hydroxychloroquine) increases the hope of a cure.