World Workshop on Oral Medicine VII: Oral adverse effects to biologic agents in patients with inflammatory disorders. A scoping review.

BACKGROUND: Biologic agents are rapidly emerging as an effective therapy to treat autoimmune and other chronic diseases. The use of these agents is poorly characterized, resulting in a lack of guidance for dental practitioners. Case reports of oral adverse events have begun to emerge. However, their scope and frequency have not been summarized and analysed to date. The objective of this review was to characterize the literature on oral adverse effects associated with biological therapy when used for autoimmune and inflammatory disorders. METHODS: This review was developed in accordance with scoping review recommendations. Search strategies were developed and employed for six databases. Studies were selected using a systematic search process but with broad inclusion of study types given the paucity of information available. Reports of oral adverse events were analysed descriptively according to agent, mechanism of action, underlying disease, and oral adverse effect observed. RESULTS: Our search returned 2080 articles and 51 met our inclusion criteria, of which most were case reports. The most frequent adverse effects included angioedema, oral lichenoid lesions, osteonecrosis of the jaw, and oral infections. There were also cases of oral malignancies associated with use of biologic agents. Less common effects such as pigmentation were also described. CONCLUSIONS: Oral adverse events have been reported in patients on biologic therapy, albeit in small numbers to date. This limits the generalizability of these results, which should not be used to generate a clinical guideline as they are based primarily on case reports. However, this study presents the first review characterizing the adverse effects observed. Large multi-center studies will be necessary to further define the oral and dental complications caused by biologic agents.

Influence of topical corticosteroids on malignant transformation of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is considered an oral potentially malignant disorder. While OLP has been associated with the development of oral squamous cell carcinoma (OSCC), little is known about the role of topical corticosteroids therapy (TCT) in the promotion of carcinogenesis. The study aimed to determine if TCT influences the time of malignant transformation of OLP to OSCC. The study also investigates this correlation in the presence or absence of Candida overgrowth, and in the context of conventional OSCC risk factors such as smoking, alcohol use, and male gender. METHODS: A retrospective analysis of electronic health records at a tertiary care academic medical center was performed. Patients with OLP and OSCC were considered for inclusion. The diagnosis of OLP required both clinical and histological documentation. RESULTS: Eighty-two patients met inclusion criteria, consisting of 48 women (58.25%) and 34 men (41.5%) and the mean patient age was 65.9 years (SD = 13.25). Forty-five patients (54.9%) received TCT for OLP before they developed OSCC. The time between the OLP and OSCC diagnoses increased by four years in patients who received topical steroid therapy for OLP (p < 0.001) and decreased by three years (p = 0.010) in those with Candida overgrowth. Gender, smoking, and alcohol use did not have a statistically significant influence on the time between OLP and OSCC. CONCLUSION: The management of OLP using TCT potentially delayed cancer development in our study. Conversely, it appears that Candida may play a role in the field cancerization of OLP patients.

World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS). MATERIALS AND METHODS: MEDLINE® , Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease-specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures. RESULTS: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long-term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient-reported indexes. CONCLUSIONS: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.

World Workshop of Oral Medicine VII: A systematic review of immunobiologic therapy for oral manifestations of pemphigoid and pemphigus.

OBJECTIVE: To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics. STUDY DESIGN: This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy. RESULTS: Inclusion criteria were met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab, and autologous platelet-rich plasma therapy for pemphigus vulgaris. Three non-RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality. CONCLUSIONS: Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet-rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy.

World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey.

OBJECTIVES: To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS: Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS: Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION: The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a consensus study.

OBJECTIVE: A core outcome set (COS) is the minimum agreed-on data set required to be measured in interventional trials. To date, there is no COS for oral lichen planus (OLP). This study describes the final consensus project that brought together the results of the previous stages of the project to develop the COS for OLP. STUDY DESIGN: The consensus process followed the Core Outcome Measures in Effectiveness Trials guidelines and involved the agreement of relevant stakeholders, including patients with OLP. Delphi-style clicker sessions were conducted at the World Workshop on Oral Medicine VIII and the 2022 American Academy of Oral Medicine Annual Conference. Attendees were asked to rate the importance of 15 outcome domains previously identified from a systematic review of interventional studies of OLP and a qualitative study of OLP patients. In a subsequent step, a group of OLP patients rated the domains. A further round of interactive consensus led to the final COS. RESULTS: The consensus processes led to a COS of 11 outcome domains to be measured in future trials on OLP. CONCLUSION: The COS developed by consensus will help reduce the heterogeneity of outcomes measured in interventional trials. This will allow future pooling of outcomes and data for meta-analyses. This project showed the effectiveness of a methodology that could be used for future COS development.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a systematic review of outcome domains.

OBJECTIVE: There is a lack of consensus regarding clinician- and patient-reported oral lichen planus (OLP) outcomes. The World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER) Project aims to develop a core outcome set (COS) for OLP, which would inform the design of clinical trials and, importantly, facilitate meta-analysis, leading to the establishment of more robust evidence for the management of this condition and hence improved patient care. STUDY DESIGN: Ovid MEDLINE, Embase, CINAHL, CENTRAL, and Clinicaltrials.gov were searched for interventional studies (randomized controlled trials, controlled clinical trials, and case series including ≥5 participants) on OLP and oral lichenoid reactions published between January 2001 and March 2022 without language restriction. All reported primary and secondary outcomes were extracted. RESULTS: The searches yielded 9,135 records, and 291 studies were included after applying the inclusion criteria. A total of 422 outcomes were identified. These were then grouped based on semantic similarity, condensing the list to 69 outcomes. The most frequently measured outcomes were pain (51.9%), clinical grading of the lesions (29.6%), lesion size/extension/area (27.5%), and adverse events (17.5%). CONCLUSION: As a first step in developing a COS for OLP, we summarized the outcomes that have been used in interventional studies over the past 2 decades, which are numerous and heterogeneous.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: the patient perspective.

OBJECTIVE: This study aimed to explore the lived experience of patients with oral lichen planus (OLP) and investigate what treatment-related outcomes are the most important to them and should be included in a core outcome set (COS) for OLP. STUDY DESIGN: A qualitative study involving focus group work with 10 participants was conducted. Interviews with each focus group were held twice: session 1 explored the lived experience of patients with OLP, and session 2 allowed patients to review a summary of the outcome domains used in the OLP literature to date. The discussions were recorded, transcribed verbatim, and analyzed using framework analysis. RESULTS: In session 1, 4 themes and 8 sub-themes emerged from the data analysis. An additional outcome, 'knowledge of family and friends,' was suggested in session 2. CONCLUSIONS: We have gained valuable insight into the lived experience of patients with OLP via this qualitative study. To our knowledge, this study is the first to explore the patient perspective on what should be measured in clinical trials on OLP, highlighting an important additional suggested outcome. This additional outcome will be voted upon in a consensus process to determine a minimum COS for OLP.

Analysis of clinical oral medicine practices at the University of Pennsylvania: a 5-year retrospective study.

OBJECTIVE: The aim of this study was to characterize oral medicine (OM) clinical practices at the University of Pennsylvania (Penn), determine the importance of OM clinical services, and emphasize aspects of training for OM specialists. STUDY DESIGN: Nonprobability sampling of OM resident patient logs for patients receiving clinical care from 2008 to 2013 was conducted. OM resident patient logs included clinical diagnosis, International Classification of Diseases, ninth edition code, medical history, clinical procedure, Current Procedural Terminology code, attending physician, and resident participation notes. RESULTS: Outpatients in OM medical practices (n = 6024) averaged 1.56 diagnoses from OM specialists. Orofacial pain (45.02%) and oral mucosal diseases (34.28%) comprised the majority of OM diagnoses. The most common procedures were tissue biopsies (59.34%) and treatments for temporomandibular disorders (29.9%). Inpatients (n = 313) comprised 3.46% of Penn OM hospital services, and cardiovascular disorders (38.99%) were the most common admitting diagnoses in this group. In the OM dental practice (n = 1648), 42.05% of patients had a median of 3 medical comorbidities (range = 2-11), of which cardiovascular disorders (27.13%) were most prevalent. CONCLUSIONS: Analysis of Penn OM clinical practices emphasizes the breadth and multidisciplinary nature of OM services and importance of comprehensive postdoctoral training in all domains of OM.

The Global Footprint of Oral Medicine Specialists: The University of Pennsylvania Experience.

The aim of this study was to analyze the global footprint of oral medicine specialists who graduated from the University of Pennsylvania oral medicine residency program. In 2016, a cross-sectional electronic survey was distributed to 53 graduates of that program, asking about their current geographical location and professional status. Of those 53 graduates, 23 (43%) completed the survey with 22 reporting their current location and 21 reporting their current professional status. The results showed that 17 graduates were located within the U.S., and five were located internationally. Twelve graduates were in full-time academic positions, three were in part-time academic positions/part-time private practice, three were in full-time private practice, two were in postdoctoral training programs, and one was not employed. This study found that oral medicine specialists trained at the University of Pennsylvania were located both domestically and internationally. The majority held faculty positions at academic institutions with fewer involved in private practice. This program may thus be considered a source of future dental academicians.

Recurrent aphthous stomatitis.

The cause of recurrent aphthous stomatitis (RAS) remains unknown despite considerable research. This article reviews the evidence for current theories regarding this disorder, including possible suspected relationships with microbial and immunologic factors, and presents medical diseases that mimic RAS lesions in certain patients. Topical management of the common form of minor RAS is described along with systemic therapy currently available to patients with severe forms of this disease.

World Workshop on Oral Medicine VI: Patient-reported outcome measures and oral mucosal disease: current status and future direction.

OBJECTIVE: This systematic review aimed to (1) explore the patient-reported outcome measures (PROMs) currently used in the oral mucosal disease literature and report on the type and context of the use of these instruments and (2) provide a future direction for PROMs in Oral Medicine practice and research. STUDY DESIGN: A systematic review of published English-language articles relating to the use of PROMs in the oral mucosal diseases literature was performed in November 2013. RESULTS: In total, 131 articles met the inclusion criteria; these articles addressed the following oral mucosal conditions: lichen planus (75); recurrent aphthous stomatitis (30); mucous membrane pemphigoid/pemphigus vulgaris (14); orofacial granulomatosis (1); and multiple oral mucosal diseases (11). The most commonly used instruments were visual analog scales (VAS) and the oral health impact profile (OHIP). CONCLUSIONS: Limited progress has been achieved with use of PROMs in Oral Medicine in the last few decades in both clinical practice and a research setting. With the engagement of allied medical disciplines in PROM usage and the promotion of PROMs by national health care bodies globally, advancement of PROMs is imperative for Oral Medicine. Exposure through the World Workshop on Oral Medicine (WWOM), along with potential involvement in the Core Outcome Measures in Effectiveness Trials (COMET) or other such initiatives, will enable worldwide collaboration to promote the development and utilization of valid and reliable PROMs in oral medicine, and improve patient care.

Update on herpesvirus infections.

Herpesviruses are responsible for many illnesses that affect the oral and maxillofacial region. The most common of these are primary or recurrent HSV infection, but knowledge of the manifestations of the eight herpesviruses that cause infections in humans will provide clinicians with a better understanding and basis for diagnosing and managing patients with these diseases. Immunocompromised patients are at greater risk for serious illness: therefore, clinicians treating transplant patients, patients receiving cancer chemotherapy, or HIV-infected individuals should be aware of the various clinical manifestations of infection with herpesviruses.

Seizure disorders: update of medical and dental considerations.

Seizure disorders and epilepsy represent neurologic conditions that commonly are seen among patients requiring dental treatment. When dentists possess a working knowledge of seizures, in addition to an understanding of updated therapies for seizure management and oral complications associated with pharmacological therapy, they are able to treat patients with these disorders more effectively. Neurologic consultations and selecting an appropriate venue for treatment may need to be addressed prior to treatment, depending on the level of seizure control. Laboratory tests designed to evaluate medication levels, leukocyte counts, and clotting ability also may be required. Frequent recall visits may be necessary for seizure disorder patients who display adverse oral complications from medication, such as gingival hypertrophy, xerostomia, and oral yeast infections.

Recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease affecting the oral mucosa. RAS occurs mostly in healthy individuals and has an atypical clinical presentation in immunocompromised individuals. The etiology of RAS is still unknown, but several local, systemic, immunologic, genetic, allergic, nutritional, and microbial factors, as well as immunosuppressive drugs, have been proposed as causative agents. Clinical management of RAS using topical and systemic therapies is based on severity of symptoms and the frequency, size, and number of lesions. The goals of therapy are to decrease pain and ulcer size, promote healing, and decrease the frequency of recurrence.

Temporomandibular disorders: evaluation and management.

Temporomandibular disorders remain a common cause of visits to primary care physicians, internists, pediatricians, and emergency departments. Advances in the clinical diagnosis, radiographic imaging, and classification of these disorders have improved long-term management. There are several types of disorders of the masticatory muscles and the temporomandibular joint as well as associated structures and each may have a complex cause, clinical course, and response to therapy. Host susceptibility plays a role at several stages of these disorders. Future research offers greater possibility in defining this heterogeneous group of disorders and providing more focused and effective treatment strategies.

Reliability and validity of mobile teledermatology in human immunodeficiency virus-positive patients in Botswana: a pilot study.

IMPORTANCE: Mobile teledermatology may increase access to care. OBJECTIVE: To determine whether mobile teledermatology in human immunodeficiency virus (HIV)-positive patients in Gaborone, Botswana, was reliable and produced valid assessments compared with face-to-face dermatologic consultations. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study conducted in outpatient clinics and public inpatient settings in Botswana for 76 HIV-positive patients 18 years and older with a skin or mucosal condition that had not been evaluated by a dermatologist. MAIN OUTCOMES AND MEASURES: We calculated the κ coefficient for diagnosis, diagnostic category, and management for test-retest and interrater reliability. We also determined sensitivity and specificity for each diagnosis. RESULTS: The κ coefficient for test-retest reliability ranged from 0.47 (95% CI, 0.35 to 0.59) to 0.78 (0.67 to 0.88) for the primary diagnosis, 0.29 (0.18 to 0.42) to 0.73 (0.61 to 0.84) for diagnostic category, and 0.17 (-0.01 to 0.36) to 0.54 (0.38 to 0.70) for management. The κ coefficient for interrater reliability ranged from 0.41 (95% CI, 0.31 to 0.52) to 0.51 (0.41 to 0.61) for the primary diagnosis, 0.22 (0.14 to 0.31) to 0.43 (0.34 to 0.53) for diagnostic category, and 0.08 (0.02 to 0.15) to 0.12 (0.01 to 0.23) for management. Sensitivity and specificity for the top 10 diagnoses varied from 0 to 0.88 and 0.84 to 1.00, respectively. CONCLUSIONS AND RELEVANCE: Our results suggest that while the use of mobile teledermatology technology in HIV-positive patients in Botswana has significant potential for improving access to care, additional work is needed to improve the reliability and validity of this technology on a larger scale in this population.