What Are Canker Sores?

This JAMA Patient Page describes the types of canker sores and how they can be treated.

Adult-Onset PFAPA Syndrome: Successful Management with Colchicine.

BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory fever syndrome primarily seen in children under age 5 years, and its etiology is unknown. Most cases are resolved by the age of 10 years, and it is rare in adults. PFAPA is characterized by recurrent episodes of fever associated with pharyngitis, stomatitis, and cervical adenitis, although not all clinical features are present at initial evaluation. Diagnosis is made clinically, as there are no specific biomarkers available. Treatment includes prednisone, colchicine, interleukin-1 blockers, and tonsillectomy. We report a case of adult-onset PFAPA syndrome that responded to colchicine. CASE REPORT A 22-year-old woman presented to the Rheumatology Clinic for evaluation of recurrent fevers associated with sore throat and enlarged painful cervical lymph nodes. She was symptom-free between the episodes. Workup for infectious causes and autoinflammatory/autoimmune diseases was unremarkable. Various differential diagnoses were considered, due to her unusual presentation. After all were ruled out, PFAPA was diagnosed based on her symptoms, and she started steroids, to which she had a dramatic response and resolution of symptoms. She was then transitioned to oral colchicine, which significantly decreased flare frequency. CONCLUSIONS Being aware of PFAPA syndrome in adults is vital. A timely diagnosis can significantly improve a patient's quality of life. This case highlights the importance of considering PFAPA syndrome in the differential diagnosis of periodic febrile illnesses in adults and the role of Colchicine as prophylaxis. Larger studies are needed to understand etiopathogenesis better and develop other effective therapeutics.

Impact of Photobiomodulation on IL1ß and TGFß-1 concentrations in patients with aphthous stomatitis.

Laser therapy has shown effectiveness in promoting wound healing by influencing various physiological factors such as blood flow, cytokines, histamine, nerve signals, lymphocyte function, tissue oxygenation, and cell growth. This study aims to evaluate the therapeutic efficacy of Photobiomodulation (PBM) treatment, by using diode laser, in modifying the levels of interleukin-1 beta (IL1ß) and transforming growth factor beta-1 (TGFß-1) in patients diagnosed with aphthous stomatitis. A before-after interventional design was conducted over 10 months with 20 subjects. Data on demographic details and serum concentrations of IL1ß and TGFß-1 were collected pre-treatment and on Days 3 and 7 post-treatments. The intervention involved a single session of four 30-second applications of a QuickLase dual-wavelength laser operating at 980 nm. Results show significant reductions in IL1ß and TGFß-1 levels after 7 days of treatment, indicating a time-dependent effect of PBM therapy on these inflammatory markers. The findings suggest that PBM therapy holds promise as an intervention for reducing inflammation associated with aphthous stomatitis.

Evaluation of the Effects of Punica granatum Flower Tablets on Pain and Healing of Minor Recurrent Aphthous Stomatitis: A Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to determine the therapeutic effect of the Punica granatum (PG) flower on recurrent aphthous stomatitis in comparison with corticosteroid therapy. MATERIALS AND METHODS: This cross-over randomized clinical trial was conducted on the patients who had been referred to Shiraz Dental School for their RAS in 2021. All the participants used both P. granatum flower tablets and Triadent a month apart for wash-out time and all compared themselves. In the experimental group, 30 patients received pomegranate flower tablets, three tablets daily, for 6 days. In the control group, oral paste Triadent has been prescribed three times a day for 6 days. The visual analog scale (VAS) and the size of RAS were evaluated on Days 0-6. Data were analyzed by SPSS version 21. The Wilcoxon test was used. RESULTS: The mean age of participants was 27.8 ± 14.77 years old. In this study, 15 patients (50%) were men and 15 patients (50%) were women. The mean value of VAS after using prescribed treatment in both evaluated groups on all days was significantly different such that the VAS values were lower for PG flower tablets than Triadent (p value < 0.05). The size of oral lesions in participants who used PG flower tablets was significantly less than those who used Triadent on all evaluation days (p value < 0.05) except on Day 1 (p value = 0.29). The descending slope of VAS from Days 1 to 6 for both Triadent and PG flower tablet users was significant and noticeable. (p value < 0.05). CONCLUSION: According to the result of this study, both P. granatum flower tablet and Triadent are useful in reducing the size, period of healing, and VAS of patients with RAS, but the PG flower tablet is more effective.

Effectiveness of low-level laser therapy in reducing pain score and healing time of recurrent aphthous stomatitis: a systematic review and meta-analysis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common chronic inflammatory oral disease that negatively impacts the quality of life. Current therapies aim to reduce pain and healing process yet challenges such as rapid loss due to salivary flushing in topical drugs and adverse effects due to prolonged use of systemic medications require further notice. Low-level laser therapy is reported with immediate pain relief and faster healing thus preserving the potential for optimal treatment modalities. This review critically analyses and summarizes the effectiveness of LLLT in reducing pain scores and healing time of RAS. METHODS: A systematic search was conducted in ScienceDirect, PubMed, and Scopus using keywords of low-level laser therapy, photo-biomodulation therapy, and recurrent aphthous stomatitis. RCTs between 1967 to June 2022, presenting characteristics of the laser and reporting pain score and/or healing time of RAS after irradiation were included. Animal studies and recurrent aphthous ulcers with a history of systemic conditions were excluded. Studies were critically appraised using the RoB 2 tool. A meta-analysis was performed using inverse variance random effects. RESULTS: Fourteen trials with a total of 664 patients were included. Reduced pain was reported in 13 studies, while shortened healing time was presented in 4. The pooling of two studies after CO2 irradiation demonstrated faster healing time compared to placebo (MD - 3.72; 95% CI - 4.18, - 3.25). CONCLUSION: Pain score and healing time of RAS were reduced after irradiation with LLLT. RoB resulted in "some concerns" urging well-designed RCTs with larger samples to further assess each laser application for comparison. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022355737.

Evaluation of cytokine expressions in patients with recurrent aphthous stomatitis: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS). Case-control studies comparing the serum or salivary levels of cytokines between RAS patients and healthy controls were searched in PubMed, EMBASE, Web of Science, and Google Scholar prior to September 30, 2023. Cytokines produced by Th1 (interleukin [IL]-1, IL-2, IL-8, IL-12, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17A) cells were investigated. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated to detect the difference. A total of 20 studies comprising 1070 RAS patients and 536 healthy controls were included. RAS patients had significantly higher salivary levels of IL-2 (SMD = 4.15, 95%CI 0.83-7.48), IL-5 (SMD = 0.53, 95%CI 0.05-1.00), IL-6 (SMD = 0.48, 95%CI 0.12-0.84), IL-12 (SMD = 0.94, 95%CI 0.18-1.71), and TNF-α (SMD = 1.31, 95%CI 0.44-2.18) compared to healthy controls. Serum levels of IL-6 (SMD = 0.48, 95%CI 0.30-0.66), TNF-α (SMD = 0.70, 95%CI 0.22-1.17), and IFN-γ (SMD = 0.72, 95%CI 0.17-1.28) were significantly increased, while serum IL-10 levels (SMD = -2.25, 95%CI -3.99 to -0.52) were reduced in RAS patients. Patients diagnosed with major RAS had markedly elevated serum IL-8 levels (SMD = 0.39, 95%CI 0.07-0.71) and a trend toward higher serum IL-6 levels (SMD = 0.51, 95%CI -0.02 to 1.04) than those with minor RAS. In conclusion, Th1/Th2-related cytokines, especially IL-2, IL-6, and TNF-α, are involved in the pathogenesis of RAS development and progression and are potential therapeutic targets for RAS.

Antibiotic prescriptions to children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis.

AIM: To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established. METHODS: Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register. RESULTS: The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%. CONCLUSION: This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Natural and Synthetic Drugs Approached for the Treatment of Recurrent Aphthous Stomatitis Over the Last Decade.

Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.

The evaluation of depression and anxiety levels of mothers of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and familial Mediterranean fever.

OBJECTIVE: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are autoinflammatory disorders typically characterized by recurrent fever attacks. These recurrent fever attacks can lead to depression and anxiety in mothers of these patients. This study aimed to compare the depression and anxiety levels in mothers of PFAPA and FMF patients. METHODS: This study is a cross-sectional observational study. 48 mothers of children with FMF and 70 mothers of children with PFAPA participated in the study. Mothers in these two groups were compared in terms of anxiety and depression by using the validated Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). RESULTS: Depression and anxiety scores of mothers were found to be similar in FMF and PFAPA groups. Moderate or high level of anxiety was seen in 32% of mothers of patients with PFAPA and 27% of mothers of patients with FMF. 23% of mothers of patients with PFAPA were evaluated as having moderate or severe depression, and 18% of mothers of patients with FMF were evaluated as having moderate depression. There was no statistically significant difference between the duration, frequency of attacks, recurrent hospitalizations, sociodemographic characteristics, and inventory scores. CONCLUSION: Depression and anxiety scores of mothers with children diagnosed with FMF and PFAPA are similar. These two diseases affect families psychosocially at similar levels. It is important to provide psychosocial support to families.

Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications.

BACKGROUND: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. AIMS: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. METHODS: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. RESULTS: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. CONCLUSIONS: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.

Association of IL-1ß 542 T>A gene polymorphism with Recurrent Aphthous Stomatitis in Erbil City population.

Recurrent Aphthous stomatitis (RAS) is common oral mucosal condition. The pathophysiology of RAS is affected by a variety of variables, including microbial, genetic, immunological and local and systemic diseases. Interleukin IL-1ß, a cytokine that promotes inflammation, has been found in high concentrations in the circulation of RAS. The goal of current investigation was to determine whether RAS is connected with polymorphisms of the IL-1ß 542 T>A gene. A total of 60 RAS patients and 30 controls were included in the study. Biochemical investigations for determining (vitamin D, vitamin B12 and zinc) were done and genotypes of IL-1B gene polymorphisms were determined using polymerase chain reaction (PCR) and sequencing. The mean age of the participants was 30.83 ± 1.466 years (range 16 to 50). There was no significant association of SNP IL-1ß 542T>A polymorphism with RAS diseases compared to controls, in both parameters such as sex (p-value=0.495) and age groups (p-value=0.6253). There was significant difference in the occurrence of both A and T alleles between RAS patients and controls (p-value=0.0058). The mean vitamin D in both genotypes TA and TT differed significantly (p-value=0.007) but in genotype AA there was no significant difference. Significant difference was observed in zinc concentration between patients and controls (p-value=0.0031). The findings of current investigation indicate that there is a specific IL-1ß 542 T>A gene variation that is associated to the pathogenesis of RAS. Allele A was related to the risk of RAS in Erbil city population.

Hematological parameters in patients with recurrent Aphthous Stomatitis: a systematic review and meta-analysis.

OBJECTIVES: Recurrent Aphthous Stomatitis (RAS) known as recurrent aphthous ulcer is a common and painful ulcerations in oral cavity. It has been suggested that hematological parameters seems to be considered as an etiologic factor. So, this meta-analysis and systematic review was aimed to examine the relationship between RAS and hematological parameters. METHODS: Relevant studies were found using online international databases including Scopus, Science direct, Web of science (ISI), PubMed, and Google Scholar search engine between 2000 and October 2023. The quality of all papers was determined by NOS checklist. Heterogeneity between the results of primary studies was evaluated with I-square index and publication bias was performed by Egger's test and funnel plots. Also, sensitivity analysis was done to check the effect of each of the primary studies on the overall estimate. Also, the statistical analyses were done using Stata software Ver. 11. RESULTS: By combining the results of primary studies, the standardized mean difference (SMD) of vitamin B12, ferritin, folic acid, hemoglobin, iron and zinc indices with a 95% confidence interval (CI) between the case (patients with RAS) and control (Healthy) groups were estimated -0.52(-0.89, -0.14), -0.20(-0.51, 0.11), -0.42(-0.95, 0.11), -0.58(-0.90, -0.27), 0.01(-0.12, 0.15), -0.33(-0.81, 0.14) respectively. The patients with vitamin B12, ferritin, folic acid, and iron deficiencies and reduced hemoglobin (Hb) level reported 2.93(2.28, 3.78), 2.50(1.48, 4.22), 1.51(0.53, 4.29), 1.46(0.70, 3.03), and 2.14(1.38, 3.32), times more susceptible to develop RAS than healthy individuals. CONCLUSION: The results of the meta-analysis indicated that the SMD of vitamin B12 serum and Hb levels in the case group was 52%. Our result have also showed that the odds ratio of vitamin B12, ferritin deficiencies, and decreased Hb level in case group was 2.93, 2.50, and 2.14 times more than healthy group.

Common Oral Conditions: A Review.

Importance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. Observations: In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1ß (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1ß (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Conclusions and Relevance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

Network pharmacology-based strategy combined with molecular docking to explore the potential mechanism of agarwood against recurrent aphthous stomatitis.

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.

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.

Plants with Anti-Ulcer Activity and Mechanism: A Review of Preclinical and Clinical Studies.

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.