Pain Management for Dental Medicine in 2021: Opioids, Coronavirus and Beyond.

Over the past year our attention has inevitably been on the coronavirus pandemic, the health and welfare of our families, patients, and office staffs as well as the re-opening of our dental practices. In addition, the opioid crisis continues, is very likely to worsen as a result of the pandemic and continues to be a challenge to Dentistry. National public health issues and healthcare disparities continue and have created a global concern for providing evidence-based, adequate pain management in the dental setting. We have brought together a group of national thought leaders and experts in this field who will share their insights on the current state of opioid prescribing in Dentistry and describe some of the exciting work being done in advancing pain management. The learning objectives for this conference proceedings were: Describing the implications of current public health concerns for safe and effective pain management in dental medicine.Identifying risk factors and understanding the current guidelines for the use of opioid and non-opioid medications in dental medicine.Analyzing the interprofessional collaborations necessary for effective pain management in dental medicine.Recognizing the challenges and opportunities brought about by the COVID-19 pandemic for the dental profession.Applying evidence-based strategies for managing the complex pain patient in the dental setting.Appraising new and future modalities for the assessment and management of orofacial pain.

Mucocutaneous Diseases.

Mucocutaneous diseases affecting the oral cavity are predominantly immune mediated or inflammatory. Three of the most common and clinically significant conditions are reviewed in this article: lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid. Because oral manifestations may be the first or only manifestation of mucocutaneous diseases, oral health professionals play a critical role in the early diagnosis and multidisciplinary management of these conditions.

HPV-16 in a distinct subset of oral epithelial dysplasia.

Human papillomavirus (HPV) 16 is the most common high-risk HPV type identified in oropharyngeal and cervical neoplasia. Recently, HPV-associated oral epithelial dysplasia with specific histopathologic features and demographics similar to HPV-oropharyngeal carcinoma has been identified. The objective of this study was to evaluate histopathologically all cases of HPV-oral epithelial dysplasia seen in one center and identify HPV types in a subset of cases. Cases with specific histopathology for HPV-oral epithelial dysplasia that were positive both by immunohistochemical studies for p16 and by in situ hybridization for high-risk types of HPV were further analyzed using QIAamp DNA Tissue Kits (Qiagen, Hilden, Germany). DNA was extracted, amplified, and digested with restriction enzymes and run on a polyacrylamide gel. Digestion patterns were visually compared with a database of known HPV digestion patterns for identification. There were 53 specimens included in the analysis. There were 47 males and six females (7.8:1), with a median age of 55 years (range 41-81). The most common site of involvement was the tongue/floor of mouth (77% of cases). Of the 53 cases, 94% exhibited parakeratosis and/or hyperkeratosis. All the cases featured karyorrhexis, apoptosis, and characteristics of conventional carcinoma in situ. The quantity of DNA extracted was sufficient for analysis in 22 cases. HPV-16 was identified in 20/22 (91%) cases. One case was associated with HPV-33 and one with HPV-58 (5% each). Eight of the 53 cases (15%) were associated with invasive squamous cell carcinomas.

Topical Clonazepam Solution for the Management of Burning Mouth Syndrome: A Retrospective Study.

AIMS: To evaluate and compare the effectiveness of two concentrations of topical clonazepam solution in improving symptoms of burning mouth syndrome (BMS). METHODS: A retrospective chart review was conducted of patients diagnosed with BMS and managed with topical clonazepam solution between 2008 and 2015. A 0.5-mg/mL solution was prescribed until 2012, when this was changed to a 0.1 mg/mL solution. Patients were instructed to swish with 5 mL for 5 minutes and spit two to four times daily. The efficacies of the two concentrations were compared using patient-reported outcome measures at the first follow-up, including the reported percentage of improvement in burning symptoms and the change in burning severity from baseline ranked on an 11-point numeric rating scale (NRS). Response to treatment was compared between the two concentrations using Wilcoxon rank sum test. RESULTS: A total of 57 subjects were included, 32 in the 0.1-mg/mL cohort and 25 in the 0.5-mg/mL cohort, and evaluated at a median follow-up of 7 weeks. The median overall percentage improvement was 32.5% in the 0.1-mg/mL cohort and 75% in the 0.5-mg/mL cohort. The median reduction in NRS score was 0.5 points in the 0.1-mg/mL cohort and 6 points in the 0.5-mg/mL cohort. The use of either outcome measure revealed that the response to treatment with the 0.5-mg/mL solution was superior to that of the 0.1 mg/mL solution (P < .01). CONCLUSION: These findings suggest that a 0.5-mg/mL topical clonazepam solution is effective in the management of BMS. Future randomized clinical trials are warranted.

Safety and tolerability of topical clonazepam solution for management of oral dysesthesia.

OBJECTIVES: The aim of the study was to determine the absolute and relative safety of treatment with 2 concentrations of topical clonazepam solution (0.1 mg/mL, 0.5 mg/mL) for management of oral dysesthesia. STUDY DESIGN: The study was a retrospective chart review of patients diagnosed with oral dysesthesia and managed with topical clonazepam solution (swish and spit) between 2008 and 2015. The relative safety of the 2 concentrations was evaluated in terms of occurrence of adverse drug reactions (ADRs) and occurrence of change to treatment plan secondary to ADRs. RESULTS: For the study, 162 patients were included-84 patients in the 0.1 mg/mL cohort and 78 in the 0.5 mg/mL cohort, who were evaluated for a median follow-up period of 6 weeks. Thirty-eight (23%) patients developed ADRs. The most frequently reported ADR was sedation (62% of ADRs), followed by altered mental status and dizziness (7% each). Dose adjustments were required in 9 patients (6%) and treatment discontinuation in 13 (8%). ADRs were more frequently reported in the 0.5 mg/mL cohort, but no significant difference was found in terms of occurrence of ADRs, change to treatment plan secondary to ADRs, or types of ADRs (P > .05). CONCLUSIONS: Treatment with topical clonazepam solution in either 0.5 mg/mL or 0.1 mg/mL concentration appears to be safe and well-tolerated. Future prospective studies are needed to confirm this finding.

Oral Medicine referrals at a hospital-based practice in the United States.

OBJECTIVE: The objective of this study was to characterize the outpatient oral medicine (OM) clinic at Brigham and Women's Hospital (BWH), with particular emphasis on patient demographic characteristics and referral patterns. MATERIALS AND METHODS: A retrospective case record review of all initial consultations with OM experts at BWH from 2008 to 2010 was conducted. Data included demographic information, type of medical insurance, reason for referral, referring doctor's specialty, and distance between the patient's home and the referring doctor as well as BWH, number of prior doctors seen for the presenting problem (per patient report), tests ordered at the consultation visit, and clinical diagnoses. RESULTS: There were 1043 new outpatient consultation visits. Patients lived a median distance of 9.5 miles from the referring doctor and 18.9 miles from BWH and saw a median of one doctor (range 0-9) before consultation. Two thirds of patients were referred by physicians. The most common diagnoses included immune-mediated mucosal conditions (27.2%), orofacial pain disorders (25.1%), benign tumors or neoplasms (10.3%), and dysplasia and cancerous conditions (7.6%). Biopsy was the most frequent test performed at consultation. CONCLUSIONS: Patients with oral conditions often see more than one doctor, before being referred to an OM expert and typically travel twice the distance to the expert compared with that between their home and the referring doctor. Equal efforts should be made to increase awareness of the importance of the specialty of OM among dentists, physicians, and the public.

Narrow-band UVB phototherapy for management of oral chronic graft-versus-host disease.

OBJECTIVES: Oral chronic graft-versus-host disease (cGVHD) is a debilitating complication following allogeneic hematopoietic cell transplantation. The objective of this study was to evaluate the safety and efficacy of intraoral narrow-band ultraviolet B (NB-UVB) phototherapy in the management of oral cGVHD. METHODS: Patients with oral cGVHD were treated using a custom NB-UVB unit for a course of 24 phototherapy sessions. Treatments were initiated at 50 mJ/cm(2) and increased by 10% at each visit unless toxicity was noted. Toxicity and response were assessed weekly. RESULTS: Eleven patients received a median of 22 (range 4-39) NB-UVB treatments; 5 patients completed 24 treatments and elected to receive a median of 7 additional treatments. Median symptom scores (0-10) for sensitivity, pain, and dryness at baseline/end of therapy were 7.5, 3, 1, and 3, 1, 2, respectively. Taking into account all patient-reported outcomes, 7/11 patients had improvement and 2/11 worsened. At least partial improvement was reported in 8/11 patients with none reporting worsening. Overtreatment occurred in 10/11 patients with all graded mild or moderate and resolving in 1-2 days. CONCLUSIONS: Intraoral NB-UVB may be effective for management of refractory oral cGVHD. Further optimization of treatment parameters, as well as minimal erythema dose testing, and inclusion of a control arm are necessary in the consideration of future studies.

Keratosis of unknown significance and leukoplakia: a preliminary study.

OBJECTIVE: The objectives were to (1) determine the frequency of specific diagnoses in a series of white lesions, and (2) describe the nature of keratotic lesions that are neither reactive nor dysplastic. STUDY DESIGN: White lesions were analyzed and diagnosed as reactive keratoses, dysplastic/malignant, or keratoses of unknown significance (KUS). RESULTS: Of the 1251 specimens that were evaluated, 703 met criteria for inclusion, and approximately 75% were reactive, 10% dysplastic/malignant, and 14% KUS. Excluding reactive keratoses, 43% were dysplastic/malignant and 57% were KUS. CONCLUSIONS: Reactive keratoses were the most common white lesions followed by lichen planus. Dysplastic/malignant lesions constituted almost 50% of all true leukoplakias. KUS constituted the remaining cases and do not show typical reactive histopathology as well as clear dysplasia. They may represent evolving or devolving reactive keratoses but may also represent the very earliest dysplasia phenotype. Clinical findings may be helpful in differentiating the two.

Dendritic cell neurofibroma with pseudorosettes: a clinicopathologic and immunohistochemical study of 5 intraoral cases.

OBJECTIVE: We report cases of dendritic cell neurofibroma with pseudorosettes (DCNP) presenting in the oral cavity and discuss clinicopathologic and immunohistochemical features that differentiate this from other benign peripheral nerve sheath tumors. STUDY DESIGN: DCNPs were identified over a 2-year period, and history and histopathologic features were reviewed. Common nerve sheath tumors from the same period were identified and compared. RESULTS: Five intraoral cases of DCNP presented in 2 men and 3 women, with a median age of 59 years. Three presented on the buccal mucosa, and 2 presented on the tongue. Each exhibited a biphasic population of cells with pseudorosettes and strong CD57 positivity. CONCLUSIONS: With 31 cases of DCNP reported, the most common site of occurrence is now the head and neck region. DCNPs exhibit a characteristic biphasic population of cells and strong CD57 positivity. Pathologists should consider this diagnosis when confronted with unusual neural lesions.

Granulomatous foreign body reaction to dermal cosmetic fillers with intraoral migration.

OBJECTIVE: We report intraoral granulomatous foreign body reactions in patients treated with calcium hydroxylapatite (CHA) or poly-l-lactic acid (PLA). STUDY DESIGN: Clinical and histopathologic data were obtained from 25 patients who developed orofacial nodules or swelling after dermal filler injections. RESULTS: All 25 patients were women aged 35 to 78 years (median, 55 years). All had a history of injection of CHA (n = 13) or PLA (n = 12) to the lips, nasolabial area, or mental area. Two patients developed cutaneous nodules at the sites of injections; all others presented with intraoral nodules (labial/buccal or vestibular mucosa) distant from the site of injections, suggestive of filler migration. Five of 21 cases presented with pain. Histopathologically, CHA presented as a diffuse mass of mauve-gray or beige, nonrefractile spherules, and PLA as rice- or spindle-shaped, geometric, refractile bodies within circumscribed nodules. CONCLUSIONS: Cutaneous injections of CHA and PLA fillers may induce granulomatous reactions presenting as intraoral nodules distant from the injection sites.

Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes.

OBJECTIVE: Bisphosphonate-related osteonecrosis of the jaws is a well-established disorder in which patients treated with bisphosphonates develop exposed necrotic bone in the oral cavity. The objective of this study was to report staging and treatment outcomes in a large cohort of patients with bisphosphonate-related osteonecrosis of the jaws managed primarily with non-surgical measures. PATIENTS AND METHODS: A retrospective medical record review was conducted from 1998 to 2010 of all patients referred for the management of bisphosphonate-related osteonecrosis of the jaws. Clinical findings and staging were assessed at initial consultation and each follow-up visit. Management was provided to minimize symptoms and/or achieve resolution of lesions. Treatment responses were defined based on symptoms and/or change in staging. RESULTS: There were 120 records reviewed and 97 patients seen for follow-up (median 12months); 90% were cancer patients. Bisphosphonate-related osteonecrosis of the jaws was managed with observation (16%), antibiotics (55%), non-surgical sequestrectomy±antibiotics (14%), or surgery±antibiotics (14%). There were 14 patients (12%) who presented with stage 0 disease; 41%, 43%, and 5% of patients presented at stages 1, 2, and 3, respectively. Greater than 70% of patients improved, remained asymptomatic, and/or showed complete re-epithelialization when evaluated at 0-3, 3-6, 6-9, 9-12, and/or >12months. Seventeen patients developed non-infectious complications of BONJ including neuropathy (N=9), painful tongue ulcers (N=7), or pathologic fracture (N=1). Twelve patients with multiple myeloma underwent hematopoietic cell transplantation without infectious complications. CONCLUSIONS: A primarily non-surgical approach appears to be a successful management strategy for bisphosphonate-related osteonecrosis of the jaws. Overall, 71-80% of patients improved or remained asymptomatic with a median follow-up of 12months.

Human papillomavirus-associated oral intraepithelial neoplasia.

This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer.

Safety assessment of oral photodynamic therapy in rats.

Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.