Genetic Association Analysis Reveals Differences in the Contribution of NOD2 Variants to the Clinical Phenotypes of Orofacial Granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is a rare, inflammatory disorder of the mouth, in which some patients also have intestinal Crohn's disease (CD). The etiology remains largely unknown, although there is a high prevalence of atopy, and oral granulomas are also seen in other immune disorders particularly CD and sarcoidosis. We investigated whether genetic variants associated with an increased risk of CD, sarcoidosis, or atopy were also associated with susceptibility to OFG. METHODS: Patients were stratified clinically as isolated oral manifestations (OFG only) or concurrent intestinal CD (OFG+CD). We genotyped 201 patients and 1023 healthy controls for risk variants in NOD2, IRGM, IL23R, ATG16L1 (CD), BTNL2 (sarcoidosis), and FLG (atopy). The coding regions of the NOD2 gene were screened for rare, potentially pathogenic variants in OFG. RESULTS: A combined analysis of 3 CD-risk variants in NOD2 showed no association with any OFG subgroup. NOD2 p.L1007insC was associated with OFG+CD (P = 0.023) and IL23R p.R381Q with all OFG (P = 0.031). The sarcoidosis risk variant rs2076530 in BTNL2 was associated with all OFG (P = 0.013). We identified 7 rare missense NOD2 alleles in 8 individuals with OFG, 4 OFG-only patients and 4 patients with OFG+CD. There was a significant enrichment of NOD2 variants in the OFG+CD group compared to the OFG-only group (P = 0.008, common variants; P = 0.04, all common and rare variants). CONCLUSIONS: Our findings suggest that genetic variants in NOD2 are only associated with OFG in patients with concurrent intestinal disease. A genome-wide association scan is needed to fully define the genetic architecture of OFG.

The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals.

Background. A loss of mucosal tolerance to the resident microbiome has been postulated in the aetiopathogenesis of spondyloarthritis, thus the purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population. Methods. Thirty-nine participants, 17 patients with AxSpA and 22 age and gender-matched disease-free controls were recruited to the study. For patients with AxSpA, disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants underwent a detailed dental examination to assess oral health, including the presence of periodontal disease assessed using probing pocket depth (PPD). Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene. Results.Patients with AxSpA had active disease (BASDAI 4.1 ± 2.1 [mean ± SD]), and a significantly greater prevalence of periodontitis (PPD ≥ 4 mm at ≥4 sites) than controls. Bacterial communities did not differ between the two groups with multiple metrics of α and ß diversity considered. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque. Discussion. Although 16S rRNA gene sequencing did not identify specific bacterial profiles associated with AxSpA, there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA.

The lived experience of Sjögren's Syndrome.

BACKGROUND: Sjögren's Syndrome is an autoimmune exocrinopathy characterised by lymphocytic infiltration of exocrine glands in multiple sites, with dry mouth as a primary presenting symptom. Although quantitative studies have shown the negative impact of both dry mouth and Sjögren's Syndrome on patients' quality of life, no qualitative diary and interview study has been undertaken to examine the lived experience of dry mouth for Sjögren's Syndrome sufferers. The aim of this qualitative study was to provide clinicians with insight into how dry mouth can impact on the daily lives of Sjögren's Syndrome patients. METHODS: The American-European Consensus Group (AECG) Revised International Classification criteria were used to identify participants from patients seen in an oral medicine clinic. After pilot study work to test the approach, the 10 main study participants were recruited. Diary entries and semi-structured interviews were used to explore how dry mouth affects their lives. Owing to the exploratory nature of the research, thematic content analysis was applied, allowing the themes to arise naturalistically from the data without bias or elicitation. RESULTS: The data showed that it is unrealistic to understand the experience of a single symptom, but that the disease as a whole needs to be taken into perspective. The empirical evidence supported four main themes that depicted the lived experience of Sjögren's Syndrome. These included: (1) the journey to diagnosis; (2) disease impact spectrum (of dry mouth amid other symptoms); (3) interactions with healthcare professionals; and (4) the positive coping process. CONCLUSIONS: The findings revealed patients' perspectives on diagnosis, coping with dry mouth and Sjögren's Syndrome, and interaction with healthcare professionals. Dry mouth is not a trivial symptom for Sjögren's Syndrome sufferers; it has considerable impact on their day-to-day lives. Healthcare professionals need to understand patients as individuals in their environment in order to be part of the Sjögren's journey.

The prevalence of dysplasia and malignant lip lesions in transplant patients.

BACKGROUND: Solid organ transplant patients are at an increased risk of developing lip malignancies. The role of HLA mismatch as a risk factor for such changes has only been described in skin. METHODS: Lip lesions were evaluated in 403 solid organ transplant patients (immunosuppressed for at least 3 months) and findings compared to age and sex matched, otherwise healthy patients who acted as controls. HLA typing was provided for the transplant patients. All patients provided details of smoking history, alcohol consumption, skin type, as assessed by ease of burning to sunlight, and exposure to sunlight or other forms of ultraviolet radiation. RESULTS: Lip lesions were identified in 36 transplant patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or malignant changes. For the control patients, one lesion was identified as dysplastic. The prevalence of dysplastic and malignant lip lesions was significantly higher (P = 0.006) in the transplant patients when compared to controls. Risk factors for dysplastic/malignant changes in the transplant group included age (P = 0.01), smoking (P = 0.033) and HLA-B mismatch (P = 0.001). Lip covering provided a significant reduction (P = 0.045) in the development of lip changes. CONCLUSION: All transplant patients should be regularly screened for lip malignancies and consulted on smoking and sunlight exposure. HLA-B mismatch does appear to make these patients more susceptible to dysplastic/malignant changes.

Advances in gastroenterology--opportunities and challenges for the dental practitioner.

As the oral cavity marks the beginning of the gastrointestinal tract (GIT), it is not surprising that it frequently mirrors disease that occurs lower in the GIT. Increasingly, clinical signs in the oral cavity are recognized as future predictors and prognostic indicators of GIT and, indeed, other systemic disease. This paper discusses recent advances in the overlap area of Oral Medicine and Gastroenterology and the significant role of the dental practitioner in the management of these patients.

Interventions for prevention and treatment of herpes simplex virus in cancer patients.

DATA SOURCES: Relevant data was sourced using the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, CANCERLIT, SIGLE and LILACS. Searching by hand was also carried out, reference lists checked for further trials, and authors and known specialists in the field contacted to try to identify any additional published or unpublished trials. STUDY SELECTION: Randomised controlled trials that concerned treatment or prophylaxis of orofacial lesions [caused by herpes simplex virus (HSV)] in adults, children (or both) who were immunocompromised because of cancer were eligible for inclusion. Outcomes of interest were presence/ absence of clinical/ culture-positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life, and adverse effects. The reports obtained from the electronic and other forms of searches were assessed independently by the review authors. Disagreements were resolved by discussion and reasons recorded. DATA EXTRACTION AND SYNTHESIS: Authors were contacted for details of randomisation, blindness and sample demographics. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaborations statistical guidelines were followed and risk ratio values were calculated using random effects models. RESULTS: In the 17 trials, three interventions were studied: use of aciclovir, valaciclovir and prostaglandin E. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life. In the placebo-controlled trials, aciclovir was found to be effective for prevention and treatment. In comparisons of active interventions, there is no evidence of a significant difference in efficacy between valaciclovir and aciclovir, or higher doses of valaciclovir and lower doses. In the single study assessing the effectiveness of prostaglandin E for prevention, this intervention was less effective than placebo. No adverse effects were reported. CONCLUSIONS: There is evidence that aciclovir is effective at preventing and treating HSV infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that, as a prophylaxis, placebo is more efficacious than prostaglandin E. In all included trials the risk of bias was unclear.

A case of sarcoidosis presenting with diffuse, bilateral swelling of the salivary glands.

UNLABELLED: This paper reports a case of a 50-year-old male with systemic sarcoidosis presenting initially with a dry mouth and bilateral swelling of the parotid salivary glands. Sarcoidosis is a multisystem granulomatous disease in which there may be multiple exocrine involvement, including the salivary and lachrymal glands. CLINICAL RELEVANCE: The diagnosis and management of this case highlights important clinical issues for dental practitioners.

Subantimicrobial dose doxycycline in the treatment of recurrent oral aphthous ulceration: a pilot study.

BACKGROUND: Recurrent oral aphthous ulceration (ROAU) is a common problem that can result in considerable pain and distress for patients. The aim of this pilot study was to evaluate the role of subantimicrobial dose doxycycline (SDD - 20 mg doxycycline twice daily) in the management of patients with ROAU. METHODS: 50 patients with ROAU were randomly allocated to treatment with SDD or placebo for 90 days. Daily ulcer diaries were completed by the participants to record the number of new ulcers and the pain associated with the ulcers. RESULTS: There were significantly more days with no new ulcers in the SDD group (80.4 +/- 5.9) than the placebo group (69.8 +/- 18.7; P=0.04). Strong trends were observed towards fewer new ulcers per day, fewer new ulcers over the 90-day period, and more days with no pain in the SDD group compared with the placebo group (P=0.06-0.08). CONCLUSION: SDD shows promise as potential therapy in the management of ROAU, though this needs to be confirmed in further studies.

Oral mucosal and osseous disorders in frail elders.

OBJECTIVE: This paper reviews the implications of frailty for oral health in old age due to the incidence of oral pathoses following on mucosal atrophy, tooth loss, trauma from dentures, polypharmacy, malnutrition, salivary disorders, degeneration of jawbone and cancer. BACKGROUND: Frailty as a condition of old age occurs when elders have energy levels below a critical threshold, or when the social or cultural environment is limited. RESULTS: Frail elders are particularly vulnerable to pathoses, but not simply because of old age per se. Oral diseases accompanying frailty are due to a complicated mixture of biopsychosocial changes that accompany old age. CONCLUSIONS: Management of oral mucosal and osseous disorders in frail elders requires an understanding of the changes that occur with advancing age.