Th1 and Th2 polymorphisms in Sjögren's syndrome and rheumatoid arthritis.

BACKGROUND: Sjogren's syndrome is characterized by T-cell infiltration of exocrine glands leading to parenchymal destruction and impaired glandular function. This process is orchestrated by cytokines, whose secretion can be regulated by genetic polymorphisms. MATERIALS AND METHODS: The aim of this study was to investigate the influence of interleukin-6 -174G/C, interleukin-10 -1082G/A, tumor necrosis factor-α -308G/A, interferon-γ +874A/T gene polymorphisms in (RA) and secondary Sjögren's syndrome (sSS). A study sample that comprised of 138 Brazilian patients was divided into three groups: RA (n = 66), sSS (n = 20), and healthy controls - C (n = 52). Patients were subjected to Schirmer's test, unstimulated salivary flow rate, biopsy of minor salivary glands, and serological tests for diagnosing SS. Genomic DNA was obtained from saliva samples and submitted to genotyping. The association between genotypes/alelle frequency and SS susceptibility was tested, as well as their association with clinical features of SS. RESULTS: Tumor necrosis factorα (TNFα)-308GA polymorphisms differed significantly between AR, SS, and C patients (P = 0.008). IL-6 overall G carriers and TNFα A carriers had a higher risk of presenting SS (P = 0.021). IL-6 polymorphism distribution was also distinctive regarding lymphocytic infiltration at the minor salivary glands (P = 0.026) and Schirmer's test (P = 0.035). CONCLUSION: These results suggest that IL-6 -174GC and TNFα-308GA gene polymorphisms are associated with susceptibility to SS. Additionally, IL-6 polymorphism could influence lymphocytic infiltration of salivary glands and diminish lachrymal gland function.

Salivary Electrostimulation in the Treatment of Radiation Therapy-Induced Xerostomia (LEONIDAS-2): A Multicenter, Randomized, Double-Masked, Sham-Controlled, Phase 3 Trial.

PURPOSE: Radiation therapy-induced xerostomia significantly affects quality of life in head and neck cancer survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms. METHODS AND MATERIALS: This multicenter, double-masked, randomized, sham-controlled clinical trial assessed the long-term effects of a commercially available intraoral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow, and improving quality of life in individuals with radiation therapy-induced xerostomia. Using a computer-generated randomization list, participants were assigned (1:1) to an active intraoral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia visual analog scale at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and visual analog scale) and quality-of-life questionnaires (EORTC QLQ-H&N35, OH-QoL16, and SF-36). RESULTS: As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality-of-life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth subscale score of the EORTC QLQ-H&N35 in favor of the active intervention. CONCLUSIONS: LEONIDAS-2 did not meet the primary and secondary outcomes.

Human herpesvirus 8 shedding in the mouth and blood of hemodialysis patients.

In Saudi Arabia, the prevalence of transplantation-associated Kaposi's sarcoma (KS) is high, and there is disparity in the prevalence rates of human herpesvirus 8 (HHV-8) infection between patients with renal disease and the general population. It was hypothesized that oral HHV-8 transmission among patients undergoing hemodialysis treatment contributes to the high prevalence of infection in renal disease patients. The detection rates of anti-HHV8-IgG in plasma and HHV-8-DNA in CD45(+)-peripheral blood cells of 72 hemodialysis patients were compared first with those of 178 blood donors and 60 pregnant women. Between the hemodialysis patients and the apparently healthy people sampled, the detection rate of anti-HHV-8-IgG was 16.7% versus 0.4% (P < 0.001) and that of HHV-8-DNA was 4.2% versus 0.4%, (P < 0.05). HHV-8 DNA was determined in oral samples and the HHV-8 viral load measured in saliva of patients undergoing hemodialysis. The amount of virus shed into saliva ranged between 8,600 and 119,562,500 (mean: 24,009,360) genome-equivalents/ml among the five patients in whom oral HHV-8 DNA was detected. Finally, HHV-8-subgenomic sequencing was conducted which showed that orally shed HHV-8 in four patients belonged to genotype C2, and in one patient to genotypes A1 and C2. HHV-8 shed in the mouth of hemodialysis patients may be extensive and diverse. Oral fluid in addition to blood is thus a likely vehicle for transmission of HHV-8, possibly contributing to the high risk of HHV-8 infection in patients undergoing hemodialysis and to KS following immunosuppression after renal transplantation.

Oral fluid and hepatitis A, B and C: a literature review.

BACKGROUND AND AIMS: Viral hepatitis is a significant global health problem that, depending upon the virus, affects individuals of the developing and/or developed world. In recent years, there has been renewed interest in whether oral fluids can be considered as a source of viral hepatitis transmission and whether oral fluid, in particular, whole saliva, may be a useful source for viral detection as part of the diagnosis and monitoring of viral hepatitis. The aim of this article was to review current data concerning the possible carriage of the hepatitis A, B and C viruses within saliva and gingival crevicular fluid. Such knowledge will indicate if (i) oral fluid is a possible source of infection and (ii) whether oral fluid can be used for diagnosis and monitoring of viral hepatitis. DATA AND SOURCES: A literature search was conducted using PubMed (Medline), EMBASE/Excerpta medica, the Cochrane database and Scopus. The results were limited to published material after 2000. Relevant material was evaluated and reviewed. CONCLUSION: There is some evidence that hepatitis viruses A, B and C are present in oral fluids, particularly whole saliva and gingival crevicular fluid and may thus be possible sources of viral detection in clinical diagnosis and monitoring. However, the data are inconsistent and warrant the need for well-planned longitudinal studies to explore the precise frequency of oral carriage of such viruses and to determine the virological and host factors that may influence the oral presence of hepatitis A, B and C viruses.

Faculty clinical articles: a regular update for the oral healthcare team.

The Faculty of Dental Surgery of the Royal College of Surgeons of England and British Dental Journal have teamed up to provide a regular series of short articles on different aspects of clinical and academic dentistry. This series will provide concise insight into a diverse range of topics with the aim of providing regular ongoing professional development for all members of the oral healthcare team. We begin here, with a short update on the Faculty and overview of the series' aims.

In vivo evaluation of traumatic and malignant oral ulcers with optical coherence tomography: A comparison between histopathological and ultrastructural findings.

Ulcers in the oral mucosa is a relatively common, although challenging, entity in oral medicine, as it can arise due to a wide range of traumatic, infective, autoimmune, and neoplastic disorders. Although histopathology of lesional and peri­lesional tissues remains the gold standard for persistent oral breaching, optical coherence tomography (OCT) has been recently suggested as a potential ally to enhance the early or non-invasive diagnosis of likely causation. The aim of the present study was to provide an in-vivo OCT analysis and description from a sample of 70 patients affected by traumatic or neoplastic-related ulcers, located on the buccal mucosa, tongue or gingiva, and compare the OCT data with those of 20 patients with healthy oral mucosa. OCT dynamic scans revealed clear distinction of epithelial layer (EP), lamina propria (LP) of healthy buccal mucosa, gingiva, and tongue as well as allowing observation of the keratin layer in gingiva, and the subepithelial vascularization of each site. Traumatic lesions had an EP of reduced in thickness, with an irregular, if not disrupted surface. Interestingly, LP seemed to preserve its reflectiveness and vascularization only in the traumatic lesions. Among neoplastic lesions, regardless their site of onset, both EP integrity/homogeneity, and LP reflectiveness/vascularization were lost and unrecognizable when compared to their healthy counterparts. OCT scanning allowed some differentiation between traumatic and malignant ulcers and thus may a useful and non-invasive means of determining the need and/or urgency of histopathological examination of oral lesions.

Diet and halitosis.

PURPOSE OF REVIEW: The present article reviews the current knowledge of halitosis with particular emphasis upon the interplay of diet and disease of the gastrointestinal tract upon oral malodour. RECENT FINDINGS: Transient-altered breath smell usually reflects the effects of foodstuffs, whereas longstanding halitosis is almost always because of oral disease such as gingivitis or periodontitis. There is, however, increasing evidence that upper gastrointestinal tract disease may give rise to halitosis and that extracts of foodstuffs may be future therapeutic agents for the treatment of halitosis derived from the mouth or upper gastrointestinal tract. SUMMARY: There is some interplay between the halitosis and the gastrointestinal tract, and it is possible that the therapy of halitosis may be aided by investigations of the effects of foodstuffs upon bacteria that give rise to volatile sulphur compounds.

Orofacial granulomatosis: clinical features and long-term outcome of therapy.

BACKGROUND: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by persistent or recurrent soft tissue enlargement, oral ulceration, and a variety of other orofacial features. There remain few detailed reports of the clinical features and long-term response to therapy of substantial groups of patients with OFG. OBJECTIVE: The aim of this study was to determine retrospectively the clinical, hematologic, and histopathological features of a large case series of patients with OFG. In addition the long-term response to therapy was examined. METHODS: Clinically relevant data of 49 patients with OFG who attended a single oral medicine unit in the United Kingdom were retrospectively examined. The analyzed parameters included diagnostic features, clinical manifestations, and outcomes and adverse side effects of therapy. RESULTS: Labial swelling was the most common presenting clinical feature at diagnosis (75.5%), followed by intraoral mucosal features other than ulceration such as cobblestoning and gingival enlargement (73.5%). Mucosal ulceration was observed in 36.7% of patients whereas extraoral facial manifestations such as cutaneous erythema and swelling were present in 40.8% of patients. Of the 45 patients who required treatment, 24 (53.3%) were treated with topical corticosteroids/immunosuppressants only, whereas 21 (46.7%) received a combined therapy (topical plus systemic corticosteroids/immunosuppressants and/or intralesional corticosteroids). The long-term outcome analysis showed complete/partial resolution of tissue swelling and oral ulceration in 78.8% and 70% of patients, respectively. LIMITATIONS: The main limitation of the current study was its retrospective design and methodology including differences in reporting clinical features and outcome. CONCLUSIONS: OFG can show multiple facial and mucosal clinical features. Long-term treatment with topical and/or combined therapy is needed in the majority of patients. Response to therapy is highly variable even though in the long-term complete/partial disease resolution can be obtained in the majority of patients. Mucosal ulceration tends to be more recalcitrant than orofacial swelling. Adverse side effects of therapy are rare.

Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features.

Herpes Simplex Virus Type 1 (HSV-1) is a nuclear replicating enveloped virus, usually acquired through direct contact with infected lesions or body fluids (typically saliva). The prevalence of HSV-1 infection increases progressively from childhood, the seroprevalence being inversely related to socioeconomic background. Primary HSV-1 infections in children are either asymptomatic or following an incubation period of about 1 week gives rise to mucocutaneous vesicular eruptions. Herpetic gingivostomatitis typically affects the tongue, lips, gingival, buccal mucosa and the hard and soft palate. Most primary oro-facial HSV infection is caused by HSV-1, infection by HSV-2 is increasingly common. Recurrent infections, which occur at variable intervals, typically give rise to vesiculo-ulcerative lesions at mucocutaneous junctions particularly the lips (herpes labialis). Recurrent HSV-1 infection within the mouth is uncommon in otherwise healthy patients, although in immunocompromised patients, recurrent infection can be more extensive and/or aggressive. The diagnosis of common herpetic infection can usually be based upon the clinical history and presenting features. Confirmatory laboratory diagnosis is, however, required when patients are, or may be, immunocompromised.

Referrals in oral medicine.

UNLABELLED: This invited article offers dentists and dental care professionals an understanding of the most appropriate and effective way of referring patients for specialist care in oral medicine, hence enabling them to offer more effective care to patients, as well as avoiding misunderstandings. CLINICAL RELEVANCE: Referrals to a specialist can help patient management, particularly for patients who may have malignant disease (or potentially malignant disease); a complicated or serious non-malignant diagnosis (such as HIV disease or pemphigus); a requirement for treatment with potent agents or complicated equipment; extra-oral lesions; or disease that is unresponsive to treatment. It can also be useful where there is a diagnosis that is in some doubt, or a situation when the clinician (or patient) requests a second opinion or wishes to share care with the specialist.

Oral manifestations of syphilis.

The past decade has shown a significant rise in the prevalence of infective syphilis in the developed world, and striking increases in its frequency have occurred in Eastern Europe, particularly the UK, and in the US. Although oral manifestations of syphilis are most likely to be observed during secondary disease, all stages of the disease can give rise to oral lesions. Significant oral lesions such as gumma-associated bony destruction and a possible predisposition to oral squamous cell carcinoma are associated with tertiary disease. Since the prevalence of infective syphilis in heterosexuals has been increasing, there has now been a gradual rise in the number of children born with congenital syphilis. Consequently, the congenital disease gives rise to dental anomalies as well as bone, skin, and neurological anomalies of the face. The aim of this report is to review syphilis-related oral lesions, as well as to summarize the relations between human immunodeficiency virus (HIV) and syphilis.

Composition of in vitro denture plaque biofilms and susceptibility to antifungals.

The aim of this study was to investigate the composition of microcosm denture plaque biofilms and the susceptibility of Candida spp. within these biofilms to antifungal agents. An in vitro model was employed to grow oral biofilms derived from denture associated stomatitis (DAS) patient samples to assess fungal growth in the presence and absence of antifungal agents. The compositions of genera present in vitro were found to be similar to those exhibited on the mucosa and denture fitting surfaces of DAS samples. Exposure to single agents, e.g., miconazole, fluconazole or chlorhexidine did not inhibit growth of Candida spp. when used in clinically relevant doses. Combinations of miconazole and chlorhexidine, pulsed into the system to mimic patient use, did reduce bacterial and candidal growth for several days. Hence, the use of dual-therapy appeared to be useful in reducing the number of viable organisms within denture plaque grown in vitro although resistance to these agents was also evident.

Anhydrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome). A case report.

The ectodermal dysplasias (EDs) are a complex group of diseases clinically characterised by congenital absence of ectodermally derived structures. The present report details the features of a 13 year old schoolboy with the rare anhydrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

Salivary production of IgA and IgG to human herpes virus 8 latent and lytic antigens by patients in whom Kaposi's sarcoma has regressed.

IgG and IgA antibodies with specificities to a latent and a lytic antigen of human herpes virus 8 (HHV-8) were detectable in the saliva and serum of eight patients whose Kaposi's sarcoma had regressed, seven of whom were HIV-1 infected. The measurement of antibody-specific activity and secretion rate, and the detection of secretory IgA all indicate anti-HHV-8 antibody activity in saliva. The specific humoral responses possibly influence mucosal replication of HHV-8, and in turn, that of HIV.

Synergism between HIV and other viruses in the mouth.

The HIV family replicate in and are shed from the mouth. Oral sexual practices potentially contribute to the overall extent of HIV transmission, particularly if high-risk practices are not restricted. Herpesviruses and papillomaviruses that appear in the oral cavity can determine oral HIV replication. The mechanisms probably include heterologous transactivation, enhanced expression of HIV receptors and co-receptors in target cells, release of cytokines and chemokines, and production of superantigens. Oral diseases peculiar to, or more common in, the HIV-infected patient further predispose to heightened oral HIV replication and trafficking. Defining the mechanisms by which oral viruses interact with HIV in the co-infected host should permit intervention measures against oral HIV transmission to be more precisely targeted.

Prion disease: possible implications for oral health care.

BACKGROUND: Prion diseases are a group of rare fatal neurodegenerative disorders in humans and animals that are histopathologically characterized by spongiform change within the central nervous system. TYPES OF STUDIES REVIEWED: The author reviewed all available case reports and any studies of the oral aspects of prion diseases published in peer-reviewed journals and available via PubMed. He then outlined the risk of nosocomial transmission of prions in dental health care. RESULTS: Sporadic Creutzfeldt-Jakob disease, or sCJD, is the most common of the acquired human prion disorders, and it typically affects elderly people and leads to rapid death. In contrast, variant CJD, or vCJD, has affected young adults from Europe, giving rise to a slow onset disorder comprising both psychiatric and neurological upset. Oral neurological manifestations are rare and seem to occur only in people with vCJD; there are no oral mucosal or gingival manifestations of prion disease. Prions can be detected in the oral tissues--usually the gingivae and dental pulp--of animals experimentally infected with prions. In contrast, prions have not been detected in the pulpal tissue of people with sCJD, and there are no data of pulpal infection in vCJD. There also are no data suggesting that prions are transmitted easily in the dental setting, but there remains the rare risk of such transmission if appropriate infection control measures are not adhered to. CLINICAL IMPLICATIONS: Few people in the United States and worldwide have prion disease. Oral manifestations are rare. Evidence suggests that the risk of transmission and acquisition of a prion infection as a result of dental treatment is rare, if appropriate infection control measures are maintained.

Infectious hepatitis C, hepatitis G, and TT virus: review and implications for dentists.

In the past 10 years, hepatitis C and G viruses have been identified, and in the last two years a further parenterally transmitted agent, termed TT virus (TTV), has been discovered. These viruses have a worldwide distribution and frequently cause chronic infection. The purpose of this article was to promote an understanding of these viral agents and their relevance in dental practice. Infected patients may develop a chronic carrier state without clinical disease or may develop liver disease, and may have related oral conditions. Dental providers will see a growing number of patients with HCV/HGV and possibly TTV infection. All of these patients require appropriate infection control measures during dental treatment.

Dental treatment as a risk factor for hepatitis B and C viral infection. A review of the recent literature.

BACKGROUND & AIM: Patients chronically infected either with hepatitis B (HBV) or hepatitis C virus (HCV) are at increased risk of developing cirrhosis, end stage liver disease and hepatocellular carcinoma. Different risk factors were found to be associated with the transmission of these viruses in various settings. HBV and HCV transmission seems to be also acquired by non-parenteral and non-sexual routes. A large number of patients infected with HCV might have non identifiable routes of viral acquisition. Hence, viral hepatitis transmission risk factors identification is the main way to reduce infection. Dental treatment may be one of such risk factors, and this aspect is addressed in the present literature review, drawing information from existing literature. METHODS: An online database search was conducted, limited to publications from January 1999 to February 2012 on specific aspects of HBV and HCV infection, including articles on risk factors, markers of infection, dentistry, epidemiology and transmission. Relevant material was evaluated and reviewed. RESULTS: Overall, 53 studies which met the selection criteria were evaluated. Although these studies were from different geographical regions of varied socioeconomic status and study populations and assessed different dental procedures, using different types of statistical analysis, we found that, although weak, there is an all-time risk of HBV and HCV infection during dental treatment. This is more important in developing countries where the rate of hepatitis infected individuals is higher. There is a need for more studies on this subject, properly planned, controlled and analyzed. CONCLUSION: Dental treatment can be included among the risk factors of HBV and HCV infection. This risk can easily be eliminated using standard precautionary measures.

Multiple endocrine neoplasia in an orthodontic patient: Interprofessional diagnostic and treatment implications.

BACKGROUND: Multiple endocrine neoplasia, type 2B (MEN 2B), is an autosomal-dominant condition characterized by the development of multiple endocrine tumors. All affected people develop an aggressive form of medullary thyroid cancer (MTC). Without early prophylactic thyroidectomy, the prognosis for patients with MEN 2B is poor; the average age at death is 21 years. CASE DESCRIPTION: The authors present a case of a 16-year-old girl who had a diagnosis of MEN 2B and was treated successfully for metastatic MTC. CLINICAL IMPLICATIONS: Given the striking orofacial manifestations of MEN 2B (marfanoid habitus; dolichocephaly; everted and thickened lips; mucosal neuromas on lips, tongue, buccal mucosa and eyelids), dental professionals are well positioned to recognize the disorder. Early identification of patients with the condition permits screening for preclinical thyroid disease, molecular genetic testing, counseling and lifesaving thyroid surgery.

Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series.

PURPOSE: To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw-a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration. METHODS: Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters. RESULTS: The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6). CONCLUSIONS: Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.