Smokeless tobacco- and quid-associated localized lesions of the oral cavity: A cross-sectional study from a dental institute.

BACKGROUND: There is a well-established link between the use of smokeless tobacco (ST) and the development of oral cancer. This study was conducted to evaluate the impact of tobacco use, quid use, and other adverse habits related to smoking and alcohol consumption on ST-induced localized lesions. OBJECTIVES: The aim of the study was to examine the demographic data, frequency and contact duration of ST on the lesion, as well as to conduct a clinical evaluation of these parameters. MATERIAL AND METHODS: A total of 13,442 patients who had been experiencing oral and dental symptoms for a period of at least 6 months were screened. Of these, 334 patients were diagnosed with STor quid-induced localized lesions and had a positive history of ST or quid use. A structured questionnaire was employed to conduct interviews with participants regarding their use of ST and other adverse habits, including smoking and alcohol consumption. Other information related to the use of ST or quid and clinical findings were also recorded, along with the patients' demographic details. A statistical analysis was carried out using the χ2 test and the regression analysis. RESULTS: The overall prevalence of ST-induced localized lesions was found to be 2.48%. In the study population, the majority of participants (58.7%) reported a habit of using khaini, while 26.8% reported using gutkha. The study found significant differences in the severity of ST-induced localized lesions and contact duration, frequency of the habit, and the presence of additional habits such as smoking and/or alcohol consumption. Based on this study, we proposed a modified Greer and Poulson's classification of ST-induced lesions, dividing them into 4 clinical types. CONCLUSIONS: Smokeless tobacco-induced localized lesions frequently remain asymptomatic, with patients unaware of their presence. Other adverse habits, including smoking and alcohol consumption, as well as increased ST contact duration were associated with the development of more severe ST-induced localized lesions.

Evaluation of oral complications in children undergoing chemotherapy: An observational study.

BACKGROUND: Chemotherapy, a cornerstone treatment for childhood cancers, can negatively impact oral health. This study aimed to evaluate the prevalence and evolution of oral complications in these patients. MATERIALS AND METHODS: A prospective observational study enrolled 44 children diagnosed with malignancy undergoing chemotherapy at a tertiary care institute in central India. Oral examinations were performed at baseline, with follow-ups at 3-6 and 9-12 months. Data collected included demographics, medical history, oral hygiene practices, and oral lesions. Blood counts and World Health Organization grading for mucositis were used. Descriptive statistics and appropriate statistical tests analyzed the data (P ≤ 0.05). RESULTS: Acute lymphoblastic leukemia (ALL) was the most prevalent malignancy. Children reported various oral complaints such as ulcers, bleeding gums, and difficulty eating. Mucositis prevalence significantly decreased over follow-up visits (baseline: 56.8% and second follow-up: 13.3%). Gingival inflammation was present, though mean scores decreased over time. Oral hygiene scores varied without significant changes. Caries experience scores increased from baseline to follow-up. CONCLUSION: This study identified a high prevalence of ALL and diverse oral complications in children undergoing chemotherapy. While mucositis severity lessened over time, other issues such as caries persisted. These findings highlight the critical need for preventive oral care strategies to safeguard this vulnerable population's oral health.

Oral mucosal changes caused by nicotine pouches: case series.

Oral nicotine pouches are the latest products in the tobacco industry. They are manufactured by large tobacco companies and entice tobacco or nicotine addicts, although the products are presented as a 'harmless choice.' Nevertheless, dentists and oral health specialists worry about oral mucosal changes due to product interactions with the oral mucosa. Unfortunately, there are no case reports of oral mucosal changes from nicotine pouches that are also investigated histopathologically. The aim of the present study was to visually and histopathologically investigate oral mucosal changes in nicotine pouch users. An online retrospective survey regarding medical and dental health, dietary habits, and tobacco consumption habits was conducted (n = 50). Respondents were selected for further intraoral and histopathological investigation based on the inclusion criteria. All five respondents had oral lesions that were histopathologically analyzed. Visually, the lesions varied in form and intensity, but all appeared white at the location where the pouches were placed. Histopathological analyses revealed parakeratosis with acanthotic epithelium, intraepithelial and connective tissue oedema, and chronic inflammatory infiltration with lymphocytes and macrophages. Participants received information about nicotine cessation and oral health recommendations. In conclusion, nicotine pouches significantly impacted oral mucosa with white lesions that revealed important changes at the cellular level.

What is the impact of nicotine pouches on oral health: a systematic review.

BACKGROUND: Increase in nicotine pouch (NP) users, particularly among the young, is a matter of concern requiring a comprehensive understanding of its short- and long-term oral health implications. The objective of this research was to systematically review potential oral side-effects associated with NP usage. METHODS: This systematic review was conducted following the PRISMA guidelines. Databases (Medline via PubMed, Scopus, Cochrane Trial, and Google Scholar) were searched for relevant studies up to February 2024. Modified Newcastle-Ottawa Scale (NOS) and the Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool were used to assess the quality and bias of the included studies. RESULTS: Three studies were included for this review, two from Europe and one from USA, and considered of a total of 190 participants. All studies were deemed to have a high risk of bias. Participants used NP for periods ranging from 1 month to 10 years. Among these studies, only one study provided information on the usage pattern between 1 and 5 units for an average of 11 ± 7 min per session. Oral mucosal changes at the site of placement were common among NP users. Oral lesions varied from slight wrinkling to various white lesions, seemingly related to the NP units consumed per day and their duration of usage. Other oral side effects included dry mouth, soreness, gingival blisters, and a strange jaw sensation. CONCLUSIONS: Research on the use of NP and its effect on oral health are currently limited. The use of NP should take into consideration the short-and-long-term effects, especially on oral health. Further studies are crucial to understand oral health implications associated with NP usage. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration number CRD 42,024,500,711.

MASCC/ISOO Clinical Practice Statement: Management of oral complications of targeted therapy.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral complications of targeted therapy. METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. Targeted agents were identified using the National Cancer Institute's list of Food and Drug Administration approved targeted therapy drugs. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: Oral toxicities secondary to targeted therapy include various mucosal conditions, gingival conditions, jawbone disease, dysesthesia, taste change, and dry mouth. For the purpose of this CPS, we focused on oral mucosal conditions, gingival conditions, taste change, and dysesthesia. The treatment of oral toxicities depends on the symptom severity. Topical steroids and immunomodulators are often used as first-line therapy for oral mucosal toxicities. Treatment approaches for oral dysesthesia and taste change primarily revolve around symptoms management. Typically, therapy protocols align with the therapeutic algorithms employed for other neuropathic pain conditions, incorporating topical pharmacological interventions to achieve relief. Other oral toxicity requires a more specific approach. CONCLUSION: Management of oral toxicities from targeted molecular therapies is designed to alleviate patient discomfort and optimize treatment outcomes. Collaboration between medical and oral health professionals is necessary for best management practices.

Oral lesions associated with imatinib mesylate therapy: five new cases and a literature review.

This study aimed to report the collective clinical characteristics of oral side effects associated with imatinib therapy according to age, sex, and clinical condition. A bibliographic review was performed using the PubMed, Web of Science, Scopus, Cochrane Library, and Embase databases. Forty-five cases of oral side effects due to imatinib therapy were identified in the literature. With the addition of five new cases seen at the authors' institution, a total of 50 cases were analysed. Of the five new cases, four with gastrointestinal stromal tumours developed oral lichenoid lesions (OLLs), and one with chronic myeloid leukaemia (CML) developed oral hyperpigmentation (OHP). Of the total 50 patients, 26 were male and 24 were female, and age ranged from 29 to 86 years. Most patients were ≥50 years old (80%); only three patients were jaw was the least common, with just five cases (10%). Among the patients with OHP, the predominant clinical condition was CML (22 cases, 91.7%). In conclusion, the possibility of oral side effects needs to be considered during the examination of patients receiving imatinib therapy.

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.