Thalidomide for management of refractory oral mucosal diseases.

BACKGROUND: Thalidomide has anti-inflammatory properties and has been used off-label for multiple mucocutaneous disorders, but its application in managing refractory oral mucosal diseases is unclear. This study aimed to review the efficacy and safety of thalidomide in treating various oral mucosal disorders refractory to conventional therapies. METHODS: The medical records of patients who were prescribed thalidomide from 2002 through 2021 for oral mucosal disorders were reviewed. Data collected included demographic characteristics, oral mucosal disease diagnosis, treatment courses, and thalidomide dose, duration, response, and side effects. RESULTS: Thalidomide was prescribed for 28 patients with diagnoses of recurrent aphthous stomatitis (n = 14), inflammatory oral lichenoid lesions (n = 6), traumatic ulcerative granuloma with stroma eosinophilia (n = 5), chronic radiation-induced mucositis (n = 2), and orofacial granulomatosis (n = 1). Patients were treated for a median duration of 84 days (range 2-1,582). Clinical improvement was observed in 19 of 22 patients who completed at least 1 cycle of thalidomide (86.4%), with complete resolution in 12 patients (54.5%). Adverse events occurred in 75% of patients (n = 21), with 8 requiring thalidomide discontinuation. The most common adverse events included peripheral neuropathy (42.9%), drowsiness (28.6%), and constipation (21.4%). CONCLUSIONS: Thalidomide may be considered for the management of refractory oral mucosal disorders. Drug side effects are common and need monitoring closely during use.

Orofacial complications from immune checkpoint inhibitors: A retrospective analysis from two academic medical centers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are FDA-approved for various cancers, yet their orofacial immune-related adverse events (irAEs) remain poorly understood. Our two-center retrospective study aims to better understand the prevalence and nature of these orofacial irAEs. METHODS: We retrospectively collected demographics, ICI details, and onset of orofacial irAEs in ICI-treated patients at University of California San Francisco and City of Hope (2013-2021). Orofacial irAEs were identified by ICD-10 codes and data categorized as dry mouth/xerostomia, oral mucosal lesions, and orofacial neuropathies. Patients with pre-existing orofacial conditions resembling the reported irAEs were excluded. RESULTS: Among 3768 ICI-treated patients, 408 (10.8%) developed 467 orofacial irAEs: oral mucosal diseases (41.4%), dry mouth/xerostomia (41.0%), and orofacial neuropathies (17.6%). Notably, head and neck cancers had the highest incidence of orofacial irAEs. CONCLUSIONS: Orofacial irAEs are relatively common in patients receiving ICIs, necessitating careful monitoring and management of these complications during and after the treatment.

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.

Orofacial lesions associated with long-term highly active antiretroviral therapy among HIV-seropositive adults in Ibadan, Nigeria.

INTRODUCTION: highly active antiretroviral therapy (HAART) has contributed to a reduction in HIV- related oral lesions and improved quality of life among HIV seropositive patients. However, the therapy is not without its side effects. This study was aimed at assessing the self- reported orofacial manifestations due to long term use of HAART, as well as the pattern of oral lesions on examination. METHODS: this was a cross-sectional study conducted among HIV seropositive adult patients in Ibadan, who had been on HAART for at least two years. Data were collected using an interviewer-administered questionnaire. Clinical diagnosis of HIV-related oral lesions was made according to the EC-Clearinghouse criteria. Data analysis was done using SPSS version 25. RESULTS: the study participants comprised of 227 HIV seropositive patients who were HAART experienced, with 54 (24%) males and 173 (76%) females. Their mean age (±SD) was 44.7 (±9.4) years. The participants CD4 count ranged from 13-1338cells/mm3, with a median count of 341 cells/mm3. About half (45%) of the participants noted one or more orofacial changes since they commenced HAART. These oral changes included dryness of mouth, burning sensation, abnormal taste, melanotic hyperpigmentation, oral thrush, ulcers, and parotid swelling. Most of those who reported oral changes had been on HAART over 10 years (p=0.03), and the changes were more reported among those on the first-line regimen. CONCLUSION: melanotic hyperpigmentation was the most common oral lesion found and burning mouth syndrome was the most commonly reported complain among HIV-seropositive adults who are on long-term HAART.

Moxifloxacin-induced oral erythema multiforme: An unusual adverse effect hitherto unreported.

Moxifloxacin is a fluoroquinolone with excellent activity in community-acquired respiratory tract infections. Common adverse effects are gastrointestinal symptoms, headache, dizziness, etc., Some serious adverse effects include tendon rupture, rhabdomyolysis, peripheral neuropathy, and interstitial nephritis. Cutaneous adverse effects include allergic reactions, angioedema, Steven-Johnson syndrome, and toxic epidermal necrosis. Erythema multiforme (EM), an acute self-limiting disease, most commonly occurs due to infection and rarely due to drugs or systemic disease. EM is classified into EM major and minor, both having skin lesions. A third category of EM has also been described with only oral involvement and without any skin lesions. Oral EM itself is an uncommon entity which has been reported due to nonsteroidal anti-inflammatory drugs. Here, we are reporting a case of moxifloxacin-induced oral EM. After extensive search in PubMed-Medline database, we could not find any such co-occurrence of moxifloxacin-induced oral EM. To the best of our knowledge, this is the first reported case.

Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity.

To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230-550 nm), zeta potential (-15 to -18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12-59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R2 = 0.972-0.976, N = 0.326-0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).

Automated read-across workflow for predicting acute oral toxicity: I. The decision scheme in the QSAR toolbox.

A decision-scheme outlining the steps for identifying the appropriate chemical category and subsequently appropriate tested source analog(s) for data gap filling of a target chemical by read-across is described. The primary features used in the grouping of the target chemical with source analogues within a database of 10,039 discrete organic substances include reactivity mechanisms associated with protein interactions and specific-acute-oral-toxicity-related mechanisms (e.g., mitochondrial uncoupling). Additionally, the grouping of chemicals making use of the in vivo rat metabolic simulator and neutral hydrolysis. Subsequently, a series of structure-based profilers are used to narrow the group to the most similar analogues. The scheme is implemented in the OECD QSAR Toolbox, so it automatically predicts acute oral toxicity as the rat oral LD50 value in log [1/mol/kg]. It was demonstrated that due to the inherent variability in experimental data, classification distribution should be employed as more adequate in comparison to the exact classification. It was proved that the predictions falling in the adjacent GSH categories to the experimentally-stated ones are acceptable given the variation in experimental data. The model performance estimated by adjacent accuracy was found to be 0.89 and 0.54 while based on R2. The mechanistic and predictive coverages were >0.85.

Performance of the GHS Mixtures Equation for Predicting Acute Oral Toxicity.

Acute oral toxicity classifications are based on the estimated chemical dose causing lethality in 50 % of laboratory animals tested (LD50). Given the large number of pesticide registration applications that require acute toxicity data, an alternative to the in vivo test could greatly reduce animal testing. The United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Mixtures Equation estimates the acute toxicity of mixtures using the toxicities of mixture components. The goal of this study was to evaluate the concordance of LD50s predicted using the GHS Mixtures Equation and LD50s from the in vivo test results. Using the EPA classification system, concordance was 55 % for the full dataset (N = 671), 52 % for agrochemical formulations (N = 620), and 84 % for antimicrobial cleaning products (N = 51). Most discordant results were from substances LD50 > 2000 mg/kg (limit test) or 2000 < LD50 < 5000 mg/kg that were predicted as LD50 > 5000 mg/kg. A supplementary analysis combining all formulations with an LD50 > 500 mg/kg produced a concordance of 82 %. The lack of more toxic formulations in this dataset prevented a thorough evaluation of the GHS equation for such substances. Accordingly, our results suggest the GHS equation is helpful to predict the toxicity of mixtures, particularly those with lower toxicity.

A case series of medication-related fibrovascular hyperplasia following hematopoietic stem cell transplantation for Fanconi anemia.

Systemic medications categorized as diphenylhydantoin, calcineurin inhibitor and calcium channel blocker may have effects on the oral cavity by modifying the inflammatory and immune response and causing undesired tissue proliferative reactions. Calcineurin inhibitors are medications commonly used for long periods in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplantation. Medication-related fibrovascular hyperplasia (MRFH) is an extra gingival hyperplastic nodular growth associated with medications use. This study reports five cases of pediatric patients (6 to 12-years-old) diagnosed with Fanconi anemia (FA) after HSCT who presented similar oral mucosal lesions associated with the use of cyclosporine, phenobarbital and amlodipine. After excision of the lesions, histopathological analysis described them as pyogenic granuloma (PG). As the aetiology of the lesions manifested by the patients was associated with the use of medications, the final diagnosis was MRFH. Despite the clinical and histopathological similarity between PG and MRFH, it is fundamental to know the aetiological agent for achieving definitive diagnosis and correct management. Considering the etiologic agent (medication) and histopathological findings, it is suggested that the most appropriate term for this manifestation should be "medication-related fibrovascular hyperplasia". The correct nomenclature related to extra gingival hyperplastic lesions identified in patients on medications with potential to induce hyperplastic reactions should be adopted to facilitate scientific communication and improve the treatment.

Oral Manifestations of Commonly Prescribed Drugs.

Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all hospital admissions. Many of the adverse drug events present intraorally or periorally in isolation or as a clinical symptom of a systemic effect. Clinical recognition and treatment of adverse drug events are important to increase patient adherence, manage drug therapy, or detect early signs of potentially serious outcomes. Oral manifestations of commonly prescribed medications include gingival enlargement, oral hyperpigmentation, oral hypersensitivity reaction, medication-related osteonecrosis, xerostomia, and other oral or perioral conditions. To prevent dose-dependent adverse drug reactions, physicians should prescribe medications judiciously using the lowest effective dose with minimal duration. Alternatively, for oral hypersensitivity reactions that are not dose dependent, quick recognition of clinical symptoms associated with time-dependent drug onset can allow for immediate discontinuation of the medication without discontinuation of other medications. Physicians can manage oral adverse drug events in the office through oral hygiene instructions for gingival enlargement, medication discontinuation for oral pigmentation, and prescription of higher fluoride toothpastes for xerostomia.

Adverse Drug Events in the Oral Cavity.

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely hyposalivation, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, reactive keratosis, dysesthesia, osteonecrosis, infection, angioedema, and malignancy.

Correlation of periodontal parameters to various types of smokeless tobacco in tobacco pouch keratosis patients: A cross-sectional study.

BACKGROUND: Tobacco practice in relation with oral diseases is a foremost cause for the global oral disease burden and is accountable for up to 50% of all periodontitis cases among adults. The present cross-sectional study was undertaken to evaluate the local effects of various types of smokeless tobacco on periodontal health in tobacco pouch keratosis (TPK) patients in Mangalore city in the state of Karnataka. MATERIALS AND METHODS: A total of 345 TPK patients were evaluated of which all were smokeless tobacco users. All the patients were clinically examined for different clinical periodontal parameters such as stains, gingival recession (GR), periodontal pocket, furcation involvement, and mobility and local effects of various types of smokeless tobacco on periodontal health in TPK sites were recorded. RESULTS: The prevalence of GR was of 87.5%. Haathichaap was the most common smokeless tobacco used (35.9%) closely followed by nonpackaged type (loose tobacco) (19.4%). This was followed by Madhu (14.2%). Likewise, periodontal parameters were observed more in these patients in decreasing order. CONCLUSION: The results of the present study agree strongly with other smokeless tobacco user studies in terms of the strong association between GR and smokeless tobacco placement. The present cross-sectional study indicates that TPK lesions are positively associated with periodontal diseases. It is important to raise awareness of both oral cancer and periodontal risks and inform about its possible health consequences thereby working towards an improvement of oral and general health and related quality of life in these patients.

Where are oral and dental adverse drug effects in product information?

OBJECTIVES: Oral adverse drug reactions are common and are associated with some of our most frequently used medicines. It is important to identify and manage oral adverse drug effects promptly as they not only negatively impact dental health, but also adversely affect medication adherence, clinical outcomes and patient quality of life. This study assessed the location of oral drug-induced adverse effects in the registered drug company product information (PI) of the top 100 most commonly used drugs in Australia as dispensed on the Pharmaceutical Benefits Scheme in 2018. METHOD: Publicly available data on dispensed medicines were accessed from the Australian Commonwealth Department of Health, to determine the top 100 medicines. The drug company PI for each of these drugs was manually searched to find their oral adverse effects. The number, type and location of the oral adverse drug reactions (ADRs) were recorded. KEY FINDINGS: Oral ADRs were commonly found varying in nature and severity. However, they were difficult to find as there is no dedicated section for oral/dental adverse effects in the PI and the section they are in is inconsistently applied. CONCLUSIONS: We recommend that regulatory authorities such as the Therapeutic Goods Administration in Australia create an additional section for oral/dental adverse effects so they are easier to find, which may assist health professionals detect recognise and report adverse drug effects manifesting in the oral cavity.

Mogamulizumab-induced Mucocutaneous Lichenoid Reaction: A Case Report and Short Review.

is missing (Short communication).

Xerogenic Medications as a Predictor for Dental Health Intervention in People with Dementia.

BACKGROUND: Older adults with dementia often have poor oral health. Chronic use of xerogenic medications may contribute to adverse dental outcomes. OBJECTIVE: To investigate the impact of xerogenic medication classes on the predicted risk for dental interventions in people with dementia. METHODS: This was a population-based cohort study involving 30,955 individuals registered in the Swedish Dementia Registry (SveDem) from 2008 to 2015. Data were linked with other national registers. The exposure was xerogenic medication classes used in the three years prior to dementia diagnosis (baseline). The primary outcome was the composite of number of tooth extractions and dental restorations over the three-year follow-up period. Secondary outcomes included the number of tooth extractions and number of dental restorations. Poisson regression models were used to estimate the association between the exposure and outcomes. Analyses were adjusted for age, gender, Mini-Mental State Examination, living arrangement, dementia disorder, average number of medications, Charlson's comorbidity index, number of dental visits, and number of teeth. RESULTS: After adjusting for potential covariates, the use of urological drugs (incidence rate ratio [IRR] 1.16, 95% CI 1.04-1.28), proton pump inhibitors (IRR 1.13, 95% CI 1.04-1.23), and opioids (IRR 1.19, 95% CI 1.06-1.34) were significantly associated with the primary composite outcome. CONCLUSION: The use of specific classes of xerogenic medications was associated with an increased risk for tooth extractions and restorations in people with dementia. The risks and benefits of xerogenic medications, in the context of oral health, should be carefully assessed in this vulnerable population.

A prospective study on oral adverse effects in head and neck cancer patients submitted to a preventive oral care protocol.

OBJECTIVE: To evaluate the occurrence and severity of oral complications, number of radiotherapy (RT) interruptions and quality of life (QoL) in a population of head and neck cancer patients receiving a preventive oral care program (POCP) and photobiomodulation therapy (PBMT). METHODS: Prospective cohort of 61 head and neck cancer patients undergoing radiochemotherapy were monitored and submitted to a POCP that included oral hygiene and plaque control, removal of infection foci, dental restorations, periodontal therapy, fluorotherapy, oral hydration, and denture removal at night, combined with daily PBMT. Outcomes included occurrence of adverse effects such as severity of oral mucositis (OM) and oral symptoms (pain, solid and fluid dysphagia, odynophagia, dysgeusia), quality of life impacts, and interruptions of radiotherapy (RT) due to symptoms. Disease-free and overall survival rates were evaluated. RESULTS: There was a significant improvement in oral health conditions between initial assessment and the two longitudinal assessments (p < 0.05), which indicates that the POCP was effective for plaque control and reduction of gingival inflammation. All participants were free of OM at the beginning of the RT regimen and only 45.9% after the 7th session, and few patients ranked the highest score of OM. For all symptoms related to OM, there was a progressive increase of severity until the 14th RT session, which remained stable until the completion of the RT regimen. The same effect was observed for the quality of life measures. Discontinued RT due to OM occurred in only three patients (5%), and the maximum duration was 10 days. The overall survival rate was 77% and disease-free survival was 73.8%. Lower survival time was observed for patients with no response to RT (p < 0.01). CONCLUSIONS: The findings of this study suggest a positive effect of an oral preventive care program for head and neck cancer patients submitted to RT. The PBMT associated with a rigorous POCP resulted in satisfactory control of oral adverse effects, reduction of quality of life impacts, and interruption of RT regimen due to severe OM.