Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments. MATERIALS AND METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias. RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34). CONCLUSION: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited. CLINICAL RELEVANCE: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

Neutropenic ulcers in oncology: terminology, diagnosis, and management.

Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal ulceration. An oral ulcer can be labeled as "neutropenic" only if the patients have primary (typically congenital) or secondary neutropenia, and neutropenia is the sole causative factor. Oral mucosal ulcers observed in patients undergoing oncologic therapy may also be termed as "neutropenic ulcers", but the pathogenesis of these oral ulcers more likely involves mucosal events related to trauma, microbial factors, and direct cytotoxicity. In cancer patients, the early appearance of oral ulcers is often attributed to oral mucositis which is a condition primarily caused by the direct mucosal cytotoxicity of chemotherapeutic agents and radiation therapy. Oral ulcers that develop later during or after active cancer therapy may result from intraoral trauma and typically manifest on non-keratinized areas of the oral mucosa which are more susceptible to mucosal damage. In patients undergoing chemotherapy, factors such as disturbances in mucosal barrier function as well as bone marrow suppression lead to reduced neutrophil count and function, and can contribute to the development of oral ulcers. While the etiology of oral ulcers in cancer therapy receiving patients can vary, it is important to emphasize that the host's response plays a crucial role in the progression and repair process of these lesions. This narrative review presents the etiopathogenesis, clinical presentation, and potential management approaches for oral ulcerations in neutropenic patients, with a particular focus on clarifying the usage of the term "neutropenic ulcer" since this term lacks diagnostic specificity and can be misleading in clinical practice regarding the underlying causes and treatment strategies.

Fifteen-minute consultation: oral ulceration in children.

OBJECTIVE: To review common presentation of oral ulcers in children and discuss management of symptoms and subsequent investigation. CONCLUSION: Although a common presentation in children, diagnosis can be challenging. Thorough history taking is critical towards diagnosis and supports signposting to relevant specialities. Clinicians should be able to support first-line symptomatic management of oral ulceration.

Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

Low-level laser therapy as adjunctive treatment for a sodium hypochlorite accident: a case report.

A 39-year-old woman sought specialized treatment complaining of a large, painful oral ulcer in the right buccal vestibule after receiving emergency endodontic treatment 3 days earlier. The patient reported that the tooth, the mandibular right first premolar, was not isolated with a rubber dam and that she felt the extrusion of a liquid in the buccal tissues. Clinically, a necrotic area with raised erythematous borders was observed in the mandibular right side. The clinical diagnosis was a chemically induced ulcer caused by a sodium hypochlorite accident. Dexamethasone and amoxicillin were prescribed to control pain and prevent secondary infection. The large size of the lesion was an indication for application of low-level laser therapy (LLLT), which was delivered at a wavelength of 685 nm (output power, 30 mW; power density, 0.5 mW/cm2 ; energy density, 6 J/cm2 ) every 2 days for a total of 6 sessions. The LLLT was applied to the necrotic area with a punctual mode (2 points) for 12 seconds per point. The patient reported a substantial reduction in pain after the second application, and the wound was completely healed after 6 sessions. The results observed in this patient suggest that LLLT could aid patients in recovering from NaOCl-related lesions.

Autologous blood as a source of platelet gel for the effective and safe treatment of oral chronic graft-versus-host disease.

BACKGROUND: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD. STUDY DESIGN AND METHODS: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS). RESULTS: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed. CONCLUSION: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment.

[Ulcerations and erosions of the oral mucosa]. / Ulcérations et érosions de la muqueuse buccale.

Ulcerations and erosions of the oral mucosa are common and occur at any age. Their knowledge and recognition are essential to ensure optimal care at the earliest stage. Etiologies are numerous and the subject of different classifications. In this work, the authors address the most frequently encountered lesions, describing their main clinical presentations. A review of treatments is then proposed.

Les ulcérations et érosions de la muqueuse buccale sont fréquentes et surviennent à tout âge. Leurs connaissance et reconnaissance sont essentielles afin d'assurer une prise en charge optimale et la plus précoce possible. Les étiologies sont très nombreuses et font l'objet de différentes classifications. Dans ce travail, les auteurs abordent les lésions les plus fréquemment rencontrées, en décrivant leurs principales présentations cliniques. Une revue des traitements est ensuite proposée.

Treatment of chemically induced oral ulcer using adipose-derived mesenchymal stem cell sheet.

BACKGROUND: This study investigated the effects of mesenchymal stem cell (MSC) sheet transplantation on healing of chemically induced oral ulceration in a rabbit animal model. METHODS: Oral mucosal ulcers were induced by topical application of filter paper soaked with 70% acetic acid to the anterior gingiva and buccal mucosa of 12 New Zealand white rabbits. The animals were randomly assigned to two groups: with (treatment group, n = 6) or without (control group, n = 6) cell sheets applied to ulcers. Gross findings were sequentially evaluated, and histologic examination was performed on day 7. RESULTS: Based on gross inspection, ulceration resolved before day 5 in the treatment group; however, in the control group, healing was incomplete on day 7. In the treatment group, the total area of the ulcer decreased significantly from day 2 to day 5 (P < 0.001) and from day 5 to day 7 (P = 0.020), whereas the area decreased significantly from day 5 to day 7 in the control group (P < 0.001). Histologic and immunofluorescence examination revealed full-thickness mucosa healing and complete basal cell coverage in the treatment group; in contrast, only partial healing was observed on day 7 in the control group. CONCLUSIONS: Cell sheet technology using MSC can be an alternative treatment for oral ulcerations in that it can decrease healing time without invasive properties.

Correction of cheek biting in a dentate patient.

Postsurgical injury by teeth to oral mucosa (reconstructed by a flap) can lead to ulceration and subsequent infection at the reconstructed site. A prompt intervention by fabricating a specially designed prosthesis to deflect the reconstruction flap away from the occluding teeth has been described for the treatment of cheek biting in the present clinical report.

Differential diagnosis and management of oral ulcers.

The diagnosis and treatment of oral lesions is often challenging due to the clinician's limited exposure to the conditions that may cause the lesions and their similar appearances. While many oral ulcers are the result of chronic trauma, some may indicate an underlying systemic condition such as a gastrointestinal dysfunction, malignancy, immunologic abnormality, or cutaneous disease. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal disease. Some of these diseases are infectious; however, most are chronic, symptomatic, and desquamative. Treatment and management requires an understanding of the immunopathologic nature of the lesion. This review will address how to differentiate and diagnose varying types of oral ulcers and provide a treatment strategy.

Diagnosing oral ulcers.

Oral ulcers are common and can have many causes, making diagnosis challenging. This article provides an overview of common oral ulcers and an algorithmic approach to establishing the correct diagnosis. Factors such as duration, pattern of recurrence, clinical appearance, mucosal location, and presence or absence of systemic symptoms are useful clues to determining an ulcer's cause.

Fifteen-minute consultation: a structured approach to the management of recurrent oral ulceration in a child.

OBJECTIVE: To present a structured approach for an outpatient consultation of a child with recurrent mouth ulcers. METHOD: Review of literature and description of approach followed in our unit. CONCLUSIONS: The literature emphasises the need to consider local and systemic causes for oral ulceration in a child. Focused history and examination are key in establishing the cause and in order to ensure appropriate management.

Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study.

BACKGROUND: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. METHODS: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. RESULTS: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. CONCLUSION: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Diagnosis and Management of Riga-Fede Disease: A Case Series.

In this case series, we present four unique cases of Riga-Fede disease (RFD), a rare disorder characterized by mucosal trauma as a result of repetitive tongue protrusion against the incisors, leading to the development of a large oral mass/ulceration. Due to the rapid development and growth of these lesions mimicking malignancy, it is important for the general and pediatric otolaryngologist to correctly diagnose and treat this benign disorder. This series highlights the variable clinical presentations, along with comorbidities of RFD, as well as the importance of interdisciplinary care between the pediatric otolaryngologist and pediatric dentist in its management. Laryngoscope, 134:4803-4805, 2024.

Recent advances in the treatment of oral ulcerative mucositis from clinical and basic perspectives.

BACKGROUND: Oral ulcerative mucositis (OUM) is common in patients with cancer, particularly in those undergoing chemoradiation therapy. The effective management of OUM is crucial for continuous cancer care and patient well-being. Recent studies have advanced our understanding of the causes, leading to clinical trials toward novel treatments. This review focuses on the contemporary therapeutic landscape, and provides the latest insights into the mechanisms of mucosal healing and pain. HIGHLIGHTS: Management strategies for OUM in patients with cancer include maintaining good oral hygiene, reducing mucosal irritation against radiation, and using various topical analgesic treatments, including herbal medicines. However, the current management practices have limitations that necessitate the development of more efficacious and novel treatments. Molecular research on transient receptor potential (TRP) channels in the oral mucosa is crucial for understanding the mechanisms of wound healing and pain in patients with OUM. Targeting TRPV3 and TRPV4 can enhance wound healing through re-epithelialization. The suppression of TRPV1, TRPA1, and TRPV4 may be effective in alleviating OUM-induced pain. CONCLUSION: Research advancements have improved our understanding and potentially led to novel treatments that offer symptomatic relief. This progress highlights the importance of collaborations between clinical researchers and scientists in the development of innovative therapies.

Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

Fever, irritability, and ulcerations in an infant.

A young infant with fever and oral ulcerations is presented herein. Extensive infectious, nutritional, immunodeficiency and autoimmune work up was performed. Pertinent maternal history suggested the potential diagnosis of neonatal Behçet's, and treatment for this condition resulted in rapid and sustained clinical improvement.

'Surviving the sting': the use of solicited diaries in children and young people with oral mucosal disease.

BACKGROUND: Chronic oral mucosal conditions, including oral ulcers, commonly affect children and young people and are capable of significant pain and morbidity. Little is known about patient perception of paediatric oral medicine services offered in relation to these conditions. The concept of a diary is increasingly recognised as a valuable way to capture patient events and perspective in healthcare research. AIM OF THE PAPER: This article provides the background to the use of solicited diaries as a method of accessing the perspective of children and young people and describes a service evaluation that aimed to explore the experiences of young people with chronic oral ulcers attending the paediatric oral medicine clinic in a UK Dental Hospital. RESULTS: Chronic oral ulcers were found to significantly impact on a variety of physical and psychosocial aspects of young people's lives. Overall, feedback regarding the specialist service was positive but suggestions were made for improvements. CONCLUSION: This article reviews the use of the solicited diary within healthcare research. It also illustrates the value of the diary in exploration of children and young people's perspective on their chronic oral mucosal disease. In addition, a need for further research in this area has been highlighted.