IntroductionBased on the FAERS database, this retrospective pharmacovigilance study analyzed gender-based reporting signals for adverse events associated with three EGFR-TKIs.MethodsAdverse drug reaction (ADR) data were collected from the FAERS database for three drugs: gefitinib (Q4 2003-Q4 2024), afatinib (Q4 2013-Q4 2024), and osimertinib (Q4 2015-Q4 2024). Reporting odds ratio (ROR) was used to detect the disproportionality signals and to assess the presence of gender differences in reporting.ResultsA total of 6,618 adverse events were reported for gefitinib (3,917 in females and 2,701 in males), 5,073 for afatinib (3,110 in females and 1,963 in males), and 18,415 for osimertinib (12,007 in females and 6,408 in males). For all three medications, the annual number of adverse drug event (ADE) reports was higher in females than in males. The ROR value and number of ADE reports under the SOC distribution indicated predominant reporting signals of skin and gastrointestinal adverse reactions. Gender-specific analysis of skin and gastrointestinal ADEs revealed that: (i) Gefitinib showed higher reporting signals for intestinal pneumatosis and skin ulcers in females; (ii) Afatinib showed higher reporting signals for acneiform dermatitis and oral pain in females, while males showed a higher reporting frequency of stomatitis and glossitis; (iii) Osimertinib showed higher reporting signals for diarrhea in females. These observed reporting disparities generate hypotheses regarding potential contributing factors, such as gender-based differences in hormone levels, gastrointestinal tract anatomy, and skin barrier function.ConclusionsThis pharmacovigilance analysis suggests the presence of sex-based reporting disparities in adverse event reports for three EGFR-TKIs. Females showed overall stronger reporting signals, with notable differences observed in specific skin and gastrointestinal events. Although the analysis has certain limitations, these findings generate hypotheses to inform future focused investigations.

Riboflavin (vitamin B2) is a water-soluble, heat-stable vitamin essential for cellular energy metabolism, acting as a precursor to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors are required by flavoproteins such as succinate dehydrogenase (Complex II), which participate in both the citric acid cycle and the mitochondrial electron transport chain, enabling adenosine triphosphate (ATP) production, maintaining redox balance, and supporting antioxidant defenses. Beyond energy metabolism, riboflavin contributes to immune function and to maintaining the health of skin, hair, and mucous membranes. Deficiency disrupts these pathways, leading to fatigue, normocytic anemia, neuromuscular symptoms, and secondary impairments in iron and other B-vitamin metabolism, including the activation of niacin (vitamin B3) and pyridoxine (vitamin B6). Because humans cannot synthesize riboflavin, adequate dietary intake is necessary, and absorption depends on normal gastrointestinal function. Excess riboflavin is excreted in urine, producing the characteristic yellow color that indicates adequate intake. Clinical deficiency is characterized by mucocutaneous manifestations (cheilosis, angular stomatitis, glossitis, dermatitis) and anemia; in severe or prolonged cases, it may lead to neurologic or ocular metabolic abnormalities, reduced physical performance, and developmental problems. Emerging evidence also links riboflavin deficiency to psoriasis, with decreased intake associated with a higher risk and upregulated riboflavin metabolism observed in psoriatic skin, suggesting a protective role for adequate riboflavin status, particularly in individuals older than 40 years. This article reviews the etiology, epidemiology, pathophysiology, clinical presentation, evaluation, management, complications, and prognosis of riboflavin deficiency. The article also highlights the roles of patient education and interprofessional healthcare team collaboration in optimizing patient outcomes.

Systemic diseases frequently manifest through characteristic oral lesions, making the oral cavity an important indicator of underlying medical conditions. Therefore, it is of interest to assess the prevalence and patterns of oral lesions among patients with confirmed systemic diseases in a hospital-based population. Hence, a cross-sectional observational analysis of 500 adults was conducted, documenting demographic data, systemic diagnoses and clinically verified oral findings, which were evaluated using WHO criteria and analyzed statistically. The results demonstrated high frequencies of periodontal disease, candidiasis, glossitis, aphthous ulcers and lichenoid reactions, with distinct associations observed between specific lesions and conditions such as diabetes mellitus, hypertension, anemia, gastrointestinal disorders, autoimmune diseases and chronic kidney disease. These findings highlight the essential role of routine oral examination in the early detection and multidisciplinary management of systemic diseases.

Twenty-two herpesviruses, all within the family Orthoherpesviridae and belonging to the Alphaherpesvirinae (n = 3) and Gammaherpesvirinae (n = 19) subfamilies have been reported in 14 different pinniped species (n = 8 phocids, n = 5 otariids and n = 1 odobenid). This review critically assessed the purported pathology reported for herpesvirus infections and found a variety of lesions present dependent on both the herpesvirus and host species. Lesions included hepatic and adrenal necrosis, interstitial pneumonia, thyroid atrophy, lymphodepletion, lymphocytolysis, ulcerative stomatitis, glossitis with tonsilitis and dermatitis, necrotizing keratitis and, potentially, other ocular lesions also. Furthermore, specific individual gammaherpesvirus infections were linked to oncogeneses including urogenital carcinoma, diffuse large B cell lymphoma and B cell lymphoblastic lymphoma. However, for many herpesvirus infections the clinical significance, lesion association and definitive herpesvirus classification remain uncertain, the latter due to lack of sufficient genome data. For these reasons, identification of the definitive host species or even if separately reported herpesviruses are actually the same virus, remain challenging. More extensive genome sequencing is required to definitively identify and classify individual herpesvirus species along with sensitive and specific tools to visualize them within tissues to enable investigation of lesion association.

Systemic diseases often have oral manifestations that can significantly impact oral health. These manifestations can stem from hematological, gastrointestinal, and viral infections, resulting in various alterations within the oral cavity. Recognizing the crucial link between general and oral health, this research aims to evaluate the awareness of dental students and interns regarding the oral manifestations of systemic diseases. A cross-sectional study involving 244 dental students, including clinical stage dental students from the Faculty of Dentistry at the University of Damascus and intern dentists, was conducted. Participants completed a survey assessing their knowledge and sources of information about oral manifestations of systemic diseases. Additionally, they answered questions pertaining to oral manifestations of gastrointestinal diseases, viral infections, and hematological disorders, alongside inquiries about investigations warranted when observing oral lesions. The participants' awareness levels were categorized as excellent, good, intermediate, or poor. Awareness levels were assessed based on the percentage of correct responses. The study demonstrated that awareness of the oral manifestations of gastrointestinal diseases ranged between intermediate and good, knowledge levels of 71.3% for inflammatory bowel diseases and 55.7% for Crohn's disease. Conversely, awareness regarding the oral manifestations of viral infections was notably lower, with poor knowledge observed for hepatitis viruses (11.5%) and COVID-19 (28.85%), while intermediate awareness was recorded for viruses associated with nasopharyngeal carcinoma (39.55%). Regarding hematological disorders, awareness was good for conditions associated with gingival bleeding (62.3%) and glossitis (70.5%). However, intermediate levels of knowledge were noted for disorders presented with aphthous ulcers (56.84%), submucosal bleeding and hemorrhagic ulcers (43.9%), and angular cheilitis (57.97%). Overall the knowledge of Syrian dental students regarding the oral manifestations of systemic diseases was classified as intermediate, with relatively strong awareness in areas such as inflammatory bowel diseases and glossitis but significant gaps in understanding viral infections and hepatitis-related symptoms. Additionally, only 11.1% of students reported having diagnosed a systemic disease based on oral manifestations, indicating a limited application of this knowledge in clinical practice. There is a need to enhance and elevate the knowledge of dental students and practitioners regarding oral lesions in general, and the oral lesions of systemic background in particular.

Vitamins are essential biocatalysts that have wide-ranging functions in supporting cellular metabolism. Vitamin deficiencies can significantly impact oral health, manifesting in oral mucosal and periodontal conditions. Deficiencies in the vitamin B complex are associated with glossitis, angular cheilitis, and recurrent aphthous stomatitis. Vitamin C deficiency leads to scurvy-related periodontal issues, whereas vitamin A insufficiency predisposes to oral epithelial keratinization abnormalities such as dry mouth and susceptibility to Candida. A reduction in vitamin D levels is linked to the risk of periodontal disease, reduced oral immunity, and oral neoplasia. Low vitamin E does not induce oral disease, but vitamin K deficiency causes gingival hemorrhage. Oral mucosal diseases have a huge impact on morbidity. We discuss the diagnostic challenges in identifying vitamin-related oral manifestations and the associated systemic features that may accompany the mucosal changes. This review provides clinicians with insight into the mechanisms that govern oral mucosal pathology and the risk factors related to specific vitamin deficiencies. The role of vitamin supplementation in treating and preventing oral conditions is also addressed.

Radiation-associated pain (RAP) after head and neck cancer treatment often results in significant discomfort, yet the mechanisms underlying this pain remain poorly understood. Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8) channels, known to mediate cold sensation, have been implicated in RAP. Previous studies suggested that inhibition of TRPM8 might offer a therapeutic approach for alleviating radiation-induced pain. We tested the effects of PBMC, a small molecule inhibitor of TRPM8, on radiation-induced glossitis and associated pain behaviors in C57BL/6J mice following tongue irradiation. We evaluated the impact of phenylethyl(2-aminoethyl)(4-(benzyloxy)-3-methoxybenzyl)carbamate (PBMC) on weight loss, burrowing, grooming behavior, and nest building. Additionally, mRNA expression of TRPM8 and other relevant ion channels was assessed in the trigeminal ganglion (TG) using qRT-PCR and in situ hybridization (ISH). Irradiated mice exhibited significant glossitis, weight loss, and altered behaviors, including impaired burrowing and grooming. PBMC treatment provided no measurable protection against glossitis and only weakly mitigated weight loss and abnormal burrowing behavior. Exposure to radiation led to downregulation of TRPM8 expression in the TG, contrasting with previous findings of upregulation. Interestingly, female mice showed greater susceptibility to RAP than males, highlighting a sex-dependent response. Our findings suggest that TRPM8 inhibition with PBMC does not alleviate radiation-induced pain or glossitis in the C57BL/6J murine model. The observed downregulation of TRPM8 expression challenges prior assumptions, and our results suggest that compensatory mechanisms or model-specific factors may contribute to the failure of PBMC to impact pain outcomes. Future studies incorporating genetic models and evaluating protein expression are necessary to better understand the role of TRPM8 in radiation-induced pain and to explore more effective therapeutic strategies.

Gastrointestinal diseases often manifest in the oral cavity, sometimes preceding systemic symptoms and serving as early indicators of underlying conditions. This review explores the oral manifestations associated with various gastrointestinal disorders, emphasizing their diagnostic significance and the importance of interdisciplinary collaboration. Diseases such as Crohn's disease, ulcerative colitis, celiac disease, gastritis, peptic ulcer disease, gastroesophageal reflux disease (GERD), and rare syndromes like Peutz-Jeghers, Gardner's, Cowden, and Plummer-Vinson are discussed in terms of their oral presentations. These include specific lesions such as lip swelling, mucositis, enamel defects, and pigmentation, as well as non-specific symptoms like aphthae, glossitis, dry mouth, and halitosis. Early recognition of oral symptoms can facilitate timely diagnosis and treatment, improving patient outcomes. Despite growing interest, further research is needed to clearly define oral manifestations across gastrointestinal diseases and enhance diagnostic protocols.