Search Results (37)

Background: Malnutrition and micronutrient deficiencies may impact the oral mucosa even before any other symptoms become clinically obvious. This makes the oral cavity an important site for early detection of nutritional imbalance. Across the literature review, the most documented vitamin is vitamin B12. Other widely reported nutrients are iron, folate, and zinc. Less consistently documented are vitamins A, C, and D. Their correlation with recurrent aphthous stomatitis (RAS), atrophic glossitis, angular cheilitis, burning mouth symptoms (BMS), mucosal erythema, and oral candidiasis (OC) is brought to light. This review collects evidence on how nutritional deficiencies influence epithelial turnover, immune competence, oxidative balance, and mucosal repair to understand the pathogenesis of oral mucosal diseases. Methods: This narrative review draws on literature searches of major databases using terms related to malnutrition, nutritional deficiencies, and oral mucosal diseases. Results: The evidence is strongest for RAS and atrophic glossitis, where several observational studies and recent systematic reviews associate hematinic deficiencies with disease presence and, in some cases, symptom improvement after performing replacement therapy. Zinc deficiency has also been linked to recurrent ulceration, burning mouth syndrome, and epithelial alterations, while vitamin B12 deficiency may present with glossitis, BMS, angular cheilitis, mucosal ulceration, and lingual linear lesions even with the absence of systemic anemia. Oral candidiasis is more common in malnourished patients due to reduced host resistance and diminished salivary protection, especially in older or medically compromised patients. Conclusions: Although causality cannot be assumed from all included studies, the literature suggests that unexplained oral mucosal lesions, especially when they are multiple or persistent, warrant nutritional screening as part of a comprehensive oral medicine assessment. Full article

Background/Objectives: The aim of this systematic review was to analyze the impact of dietary modifications on unsaturated fatty acids (UFAs) intake on the course of three oral autoimmune conditions: oral lichen planus (OLP), recurrent aphthous stomatitis (RAS), and pemphigus. These acids serve a structural function as key components of cell membrane phospholipids, influencing their fluidity and membrane receptor activity. The proper ratio of these acids in the diet may be crucial for maintaining normal functioning of the human immune system. Methods: The following bases were searched with no time restrictions: PUMS Library, Embase/Elsevier, PubMed/MEDLINE, Scopus, and Web of Science. Of the 247 results identified in pre-screening, 6 studies that met all search criteria were included in the final systematic review. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for randomized trials and the Newcastle–Ottawa Scale for non-randomized studies. Results: The outcome measures included: proportions of LA-derived oxylipins (9-HODE, 13-HODE), ulcer size (mm), monthly number of ulcers, average pain (VAS), duration of episodes, and quality of life (OHIP-14), healing time, and fatty acid analysis of total plasma phospholipid fraction, Pemphigus Disease Area Index (PDAI) for disease severity (mild ≤ 15, severe > 15); AHEI-2010 score (9–90 points) for diet quality. In all studies, improvements in clinical parameters and subjective complaints were observed after implementing a dietary intervention. Conclusions: Dietary modification may be a valuable component of adjunctive therapy. Nutritional optimization offers a genuine opportunity to reduce reliance on conventional pharmaceuticals, thereby limiting the risk of systemic adverse effects associated with long-term pharmacotherapy. Full article

Recurrent aphthous ulcers (RAU) are highly prevalent oral mucosal lesions, while current therapies are limited by short residence time and poor efficacy in the dynamic oral environment. Probiotics such as Lactobacillus reuteri (L. reuteri) exhibit antimicrobial, immunomodulatory, and tissue-repair functions; however, their direct application is restricted by low stability and retention in the oral cavity. In this study, L. reuteri-loaded sodium alginate/chitosan composite hydrogels were developed via ionic crosslinking as a bioadhesive platform for local delivery. The hydrogels exhibited well-defined porous structures, favorable viscoelastic properties, and tunable swelling and degradation behaviors under simulated physiological conditions. Importantly, the system enabled sustained probiotic release and maintained high viability during 30 days of storage. In vitro antibacterial assays demonstrated that the hydrogels effectively inhibited the growth of Staphylococcus aureus and Candida albicans. Among the formulations, the hydrogel with 10 mg·mL⁻¹ chitosan achieved an optimal balance between structural stability and mass transfer, resulting in enhanced release performance and antibacterial efficacy. Overall, this study presents a microecology-oriented hydrogel system for efficient probiotic delivery in oral environments, offering a promising bioadhesive probiotic delivery platform with potential applications in RAU management and advancing the development of bioactive, mucosa-adaptive therapeutic platforms. Full article

Background/Aim: This study aims to assess the prevalence of self-reported oral ulcers and their associated factors among patients with type 2 diabetes mellitus (T2DM) in Bangladesh. Materials and Methods: A hospital-based cross-sectional study was conducted among 260 patients with T2DM attending outpatient dental services at three tertiary hospitals in Dhaka. Data were collected using a semi-structured questionnaire covering sociodemographic characteristics, behavioral and dietary factors, medical history, and self-reported oral mucosal conditions. Associations between oral ulcers and potential risk factors were analyzed using Chi-square and Fisher’s exact tests. Results: Most participants were middle-aged (50–59 years), female, of low educational status and married, with a high prevalence of regular tooth-brushing but low use of oral hygiene aids such as mouthwash. Traumatic ulcers (21.5%) and oral lichen planus (19.6%) were the most frequently observed oral mucosal lesions followed by recurrent aphthous ulcers, oral lichenoid reactions, and oral candidiasis. Traumatic ulcers and oral lichenoid reactions showed associations with sharp teeth, dentures or braces, and amalgam restorations, while lichen planus and aphthous ulcers were significantly associated with smoking, systemic conditions such as hypertension, and coexisting oral lesions such as oral candidiasis. Multivariable logistic regression showed that sharp teeth, denture or brace use, amalgam restorations, and tobacco-related habits were associated with oral lesions. Conclusions: Oral ulcers and related mucosal lesions were found to be common among patients with T2DM in Bangladesh, with traumatic ulcers being most frequent and several local and behavioral factors showing significant associations. Full article

Background/Objectives: Encouraged by the traditional use of Cotinus coggygria Scop. (European smoketree) for its anti-inflammatory and antioxidant properties, and considering the limitations of current therapies for recurrent aphthous stomatitis (RAS), we aimed to develop and evaluate a mucoadhesive oral gel containing C. coggygria stem bark extract. Methods: A thermosensitive gel was formulated using Carbopol^® 974P NF and poloxamer 407, enriched with 5% C. coggygria extract (CC gel), and characterized for its organoleptic properties, pH, electrical conductivity, and storage stability over six months. Therapeutic efficacy was assessed in a Wistar albino rat model of chemically induced oral ulcers. Animals were divided into three groups: untreated controls (CTRL), rats treated with gel base (GB), and those treated with CC gel over a 10-day period. Healing progression was monitored macroscopically (ulcer size reduction), biochemically (oxidative stress markers in plasma and tissue), and histologically. Results: The CC gel demonstrated satisfactory physicochemical stability and mucosal compatibility. Moreover, it significantly accelerated ulcer contraction and achieved complete re-epithelialization by day 6. Biochemical analyses revealed reduced TBARS and increased SOD, CAT, and GSH levels in ulcer tissue, indicating enhanced local antioxidant defense. Histological evaluation confirmed early resolution of inflammation, pronounced fibroblast activity, capillary proliferation, and full epithelial regeneration in the CC group, in contrast to delayed healing and persistent inflammatory infiltration in the GB and CTRL groups. Conclusions: These findings indicate that the CC gel has potential as a natural, topical formulation with antioxidant and regenerative properties for RAS, although further studies, including clinical evaluation, are required to confirm its overall efficacy and long-term safety. Full article

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disorder of the oral cavity, although its etiology is still unknown. The present study aimed to identify the proteomic profile associated with the RAS inflammatory process, thereby enhancing our understanding of its etiopathogenesis. We compared salivary protein profiles of RAS patients during an active episode of oral ulceration (30 patients, mean age 36.9) to those from healthy donors without a history of RAS (30 healthy subjects, mean age 37.9). Using 2D-electrophoresis and mass spectrometry (MALDI-TOF) analysis, we identified 17 proteins that were differentially expressed in the two groups. Notably, Cystatin SN (CST1) appeared to be significantly downregulated in RAS patients. These findings were validated by Western blot analysis: CST1 was detected in only 3 of the 30 RAS cases, while it was strongly expressed in all the healthy subjects. Although preliminary, our results suggest a potential role for CST1 in the etiopathogenesis of RAS. Interestingly, the relative absence of CST1 in RAS patients seems to align with some clinical and molecular features of this disease. Full article

Background: Antiphospholipid syndrome (APS) is one of the highest risk factors for obstetric complications. This article contains a case report of a patient with obstetric APS who experienced fetal loss during their first pregnancy and experienced a successful second pregnancy upon treatment with acetylsalicylic acid (ASA), low-molecular-weight heparin (LMWH), and hydroxychloroquine (HCQ). We compare placental pathology in these two pregnancies and discuss the impact of antiphospholipid antibodies and clinical management on pregnancy outcomes. We also propose methods to monitor obstetric antiphospholipid syndrome (OAPS) patients during pregnancy. Methods: A 26-year-old woman presented with a history of stillbirth at 25 weeks of pregnancy due to placental insufficiency. Before pregnancy, she experienced symptoms suggestive of autoimmune disease (thrombocytopenia, recurrent mouth aphthous ulcers, and Raynaud’s phenomenon) but had no diagnosis. Placental dysfunction correlated with the high ratio of sFlt-1/PIGF (soluble fms-like tyrosine kinase 1 and the placental growth factors index). Laboratory tests revealed the presence of antinuclear antibodies (ANAs) and triple positivity for antiphospholipid antibodies (aPLs). Results: Following the initiation of treatment for OAPS and regular monitoring consistent with current guidelines, the patient conceived and successfully delivered a healthy child. Conclusions: Adequate therapy and close monitoring during pregnancy, including clinical observation, placental biomarkers and regular ultrasonography, may help to reduce the risks and increase chances for optimal pregnancy outcomes. Additionally, pathological examination and clinical collaboration are essential components in future pregnancy counseling and should be a part of multidisciplinary management. Full article

Background: Recurrent aphthous stomatitis (RAS) has been recognized as a pathology characterized by ulcerations of the oral mucosa with a wide cross-prevalence in the general population. The aim of the present investigation was to investigate a new gel formulation for the treatment of minor oral ulcers after 2 weeks of treatment. Materials and Methods: A randomized triple-blinded controlled trial was designed for the present purpose. A total of two different study groups was conceptualized: group I (placebo) and group II (active treatment). After the enrolment process, the subjects were included in a domiciliary treatment and evaluated by a blinded operator to clinical scoring and thermography assessment at the baseline, after 1 week, and 2 weeks. Results: A total of 60 patients were observed and treated in the present study. The mean age of the patients was 34.91 ± 7.27 years old for a total of 38 females and 22 males. At 1 and 2 weeks, a significant difference in clinical scoring was observed comparing group I and group II (p < 0.05). A significant reduction in pain score was detected in group II patients (p < 0.05) after the topical gel administration. Conclusions: According to the findings of this randomized trial, the gel treatment showed a significant decrease in the signs and symptoms of oral ulcerations and could be considered useful to ameliorate the clinical course of the disease. Full article

Glycyrrhiza glabra (licorice) has been used as an herbal medicine for a long time due to its anti-inflammatory, antioxidant, and antimicrobial properties. Additionally, multiple reports have demonstrated its ability to promote wound healing. Several randomized controlled or clinical trials (RCTs) have demonstrated its potentially therapeutic effects in oral mucosal diseases, especially in recurrent aphthous stomatitis (RAS). This systematic review aims to summarize the evidence for Glycyrrhiza glabra in treating RAS. A systematic search was performed across five databases: PubMed (Medline), ScienceDirect, Scopus document, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Library Database of Systematic Reviews. This study was reported following the PRISMA guidelines. RCT study using Glycyrrhiza glabra for treating RAS was included in this study with several reported outcomes like changes in ulcer diameter, pain, and healing periods. Seven RCTs were included, which used Glycyrrhiza glabra in the form of patches, pastes, mucoadhesive tablets, and mouthwashes for treating RAS. Glycyrrhiza glabra treatment in various regimens showed significant improvements in pain, ulcer diameter, and healing time in patients with RAS. This review suggests the potential of Glycyrrhiza glabra as an alternative treatment option for RAS. Full article

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet’s disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet’s disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. Full article

Background/Objectives: Recurrent aphthous stomatitis is a common oral mucosal disorder characterized by painful ulcerations and frequent recurrences, which can significantly impair quality of life. This study explores the efficacy of zinc-enriched multivitamin supplementation (ZnVita, containing 22.5 mg of elemental zinc) for the treatment of recurrent aphthous stomatitis in treatment-naïve patients, aiming to diminish the reliance on immunomodulatory drugs. Methods: Conducted as a retrospective observational study at a tertiary referral hospital from 2013 to 2023, we analyzed 201 patients who received ZnVita daily for a minimum duration of one month as their initial management. Patients who were using systemic immunomodulating agents or met the diagnostic criteria for Behçet’s disease were excluded. Results: Of the 201 patients, 95 presented with an oral ulcer alone and 106 exhibited additional symptoms associated with Behçet’s disease. Efficacy analysis was conducted on 155 patients due to follow-up loss or incomplete data. Among them, 58.7% (91/155) showed partial or significant responses. Patients with BD-related symptoms were significantly more prevalent among non-responders (64.1%, 41/64) compared to responders (42.9%, 39/91), with a statistically significant difference (p = 0.009). Treatment was well-tolerated, with mild gastrointestinal adverse events reported in only 2.5% of cases. Conclusions: These results suggest that zinc-enriched multivitamin supplementation offers a beneficial and safe initial treatment alternative for a considerable proportion of treatment-naïve recurrent aphthous stomatitis patients, especially those without concurrent symptoms of Behçet’s disease, showcasing its potential in reducing the future need for immunomodulatory treatments. Full article

This review’s objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in this review had to be published in English between 2017 and 2023, be original studies, and involve human subjects. Fifteen studies were included in this review: three examining oral symptoms of vitamin B12 deficiency; one assessing vitamin B complex and vitamin E for recurrent oral ulcers; one investigating serum vitamin D levels in recurrent aphthous stomatitis patients; three exploring hypovitaminosis effects on dental caries; two measuring blood serum vitamin D levels; one evaluating vitamin B12 hypovitaminosis; three investigating hypovitaminosis as indicative of gingival disease; one focusing on vitamin deficiencies and enamel developmental abnormalities; one assessing vitamin deficiencies in oral cancer patients; one examining vitamin K as an oral anticoagulant and its role in perioperative hemorrhage; and one evaluating vitamin effects on burning mouth syndrome. Despite some limitations, evidence suggests a correlation between vitamin deficiencies and oral symptoms. This systematic review was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (202430039). Full article

The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall ‘high risk’ of bias, while the remaining studies were categorised as having an overall ‘uncertain risk’. The overall certainty of the evidence was ‘very low’. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS. Full article

It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. Among the most common issues is the development of ulcers of the oral mucosa (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from those of other anti-cancer agents, occur with regularity, and impact patient outcomes. mIAS’ pathogenesis has been the subject of speculation, and its similar presentation to recurrent aphthous stomatitis (RAS) has led to the hypothesis that it might serve as a surrogate to better understand RAS. Based on a review of the literature, the current manuscript provides a hypothesis regarding the mechanisms by which mTORis uniquely initiate mucosal injury and an explanation for the observation that steroids (also an immunosuppressive) are effective in its treatment through a non-immunologic mechanism. Unexplained unique features of mIAS are discussed in this review in the context of future investigation. Full article

Celiac disease (CeD) is a chronic gluten-sensitive immune-mediated enteropathy characterized by numerous intestinal and extra-intestinal signs and symptoms. Among extra-intestinal manifestations, otorhinolaryngological (ORL) complaints in CeD are relatively rare and their relation to CeD is frequently overlooked by physicians. Recent studies underlined that the prevalence of recurrent aphthous stomatitis, aphthous ulcers, geographic tongue, and xerostomia was significantly increased in CeD patients compared with healthy individuals. However, data about the other oral manifestations of CeD, such as atrophic glossitis, glossodynia, angular cheilitis, and salivary abnormalities, are scanty. Further ORL conditions associated with CeD include sensorineural hearing loss, nasal abnormalities, and obstructive sleep apnea. Moreover, several esophageal disorders such as gastroesophageal reflux disease and eosinophilic esophagitis have been associated with CeD. The pathophysiological link between both ORL and esophageal manifestations and CeD might be further investigated. In addition, also the role of gluten-free diet in improving these conditions is largely unclear. Certainly, otorhinolaryngologists can play an important role in identifying people with unrecognized CeD and may help prevent its long-term complications. The aim of this narrative review is to analyze the latest evidence on the association between CeD and ORL and esophageal manifestations. Full article