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.

Oral lichen planus induced by long-term use of antimicrobials for recurrent aphthous ulcer: A case report and literature review. / é•¿æœŸä½¿ç”¨æŠ—èŒè¯ç‰©æ²»ç–—å¤å‘æ€§å£è ”æºƒç–¡å¼•èµ·å£è ”æ‰å¹³è‹”è—“1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

The precise etiology of oral lichen planus (OLP) is still unclear, but the existing evidence suggests that drug intake, virus infection, fungal infection, psychological disorders, and immunodeficiency are closely associated with the pathogenesis of OLP. We report a case of OLP accompanied with candidiasis induced by long-term use of antimicrobials for recurrent aphthous ulcer (RAU) and update the literature, to discuss the possible association between OLP and misuse of antimicrobials, and to inform general dentists and pharmacists the importance for practice with optimal antimicrobial stewardship. In this case, a 42-year-old man presented to Xiangya Stomatological Hospital with white reticular patterns spreading in the oral cavity for almost 1 year. He was diagnosed with OLP via histopathological examination. He had a 5-year history of RAU which occurred every 1-2 months, and he was given antimicrobials ingested or injected whenever the ulcers came up. Satisfactory treatment results were obtained by stopping the abuse of antimicrobials and local antifungal therapy. Meanwhile, the exacerbation and alleviation of OLP was closely related to the administration of antimicrobials. Combined with literature review, antimicrobial might contribute to the development of OLP by inducing candidiasis, a common side-effect of misuse of antimicrobials. Considering the seriousness of antimicrobial resistance and opportunistic infection, dentists should prescribe antimicrobials judiciously according to guidelines and evidence-based indications. Appropriate prescribing of antimicrobials is a professional responsibility to all dentists.

Thalidomide use in the management of oromucosal disease: A 10-year review of safety and efficacy in 12 patients.

OBJECTIVE: Thalidomide is an effective systemic agent in the management of ulcerative oromucosal conditions. However, its clinical use is limited because of its known adverse effect profile, including teratogenicity, peripheral neuropathy, and thromboembolic risk. The aim of this study was to review the efficacy and safety of thalidomide over a 10-year period in an Oral Medicine specialty clinic. STUDY DESIGN: Clinical records of the Oral Medicine Department at the Royal National ENT and Eastman Dental Hospitals (London, UK) were retrospectively reviewed for patients prescribed thalidomide between 2009 and 2019 for the management of oromucosal ulceration. Twelve eligible patients were identified. Data on patient response to treatment and major/minor adverse events were obtained from their clinical and electrophysiologic records. RESULTS: A complete remission rate was noted in 50% (6 of 12) patients treated for recurrent aphthous stomatitis, HIV-related ulceration and oral Crohn disease. A thalidomide-induced neuropathy rate of 41.7% (5 of 12) was detected by electrophysiology testing, however clinical symptoms of neuropathy were only described by 3 subjects. No other major adverse effects were reported. CONCLUSIONS: Thalidomide demonstrates a good efficacy-to-safety ratio in the management of oromucosal ulceration over a prolonged treatment period. Interval electrophysiologic testing is essential to monitor for thalidomide-induced neuropathy. In this cohort, neuropathy does not appear to be a dose-dependent outcome.

Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: A systematic review.

The present systematic review sought to evaluate the effects of Sodium Lauryl Sulfate (SLS)-free compared to SLS-containing dentifrices on (Recurrent) aphthous stomatitis (RAS) in patients with this condition. Cochrane, Medline (PubMed) and Embase databases, and some trial registries were searched through December 2017. There was no language, nor publication year restrictions. We included double-blinded randomized controlled trials that compared the effects of dentifrices with and without SLS on RAS in humans. Data extraction was compliant with PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. PROSPERO 2018:CRD42018086001. Four trials were included in this review (all crossover studies; n = 124 participants) and two contributed to the main meta-analysis based on the random-effect model. SLS-free dentifrice, when compared to SLS-containing statistically significantly, reduced the number of ulcers, duration of ulcer, number of episodes, and ulcer pain. Sensitivity analysis of the four studies as parallel-group trials shows a consistent direction of effect in favor of SLS-free dentifrice usage. In conclusion, the qualitative and quantitative synthesis of the eligible trials for this review showed that use of SLS-free consistently reduced all four parameters of ulcers measured. The available evidence suggests that patients with RAS may benefit from using SLS-free dentifrices for their daily oral care. However, future well-designed trials are still required to strengthen the current body of evidence.

Azithromycin-induced Aphthous Stomatitis: A Case Series.

BACKGROUND: Azithromycin is one of the most popular antibiotics in current clinical practice. This medication generally considered to be safe and well-tolerated in different demographic populations. Like any other drug, azithromycin use is not without risk and adverse effects. In recent years, cardiovascular accidents have been announced as its major and most important side effect. But azithromycin use can be accompanied with less recognized complications which are significantly discomforting. In this article, we presented a neglected adverse effect of azithromycin in medical literature which is aphthous stomatitis. METHODS: We detected three cases with this complication in our center during a one-year period. All the accessible clinical data were recorded and PubMed database was explored to assess the relevant literature. RESULTS: The patients had aphthous stomatitis within 24 hours of the first dose which was healed in about 2 to 3 weeks. Naranjo scoring system showed a probable stage for this adverse drug reaction. There was no such a report in our database search process. CONCLUSION: It could be stated that aphthous stomatitis is an important adverse effect of azithromycin that can affect the patient's quality of life during therapy and in the majority of cases, it can be neglected by healthcare practitioners.

Promote Recurrent Aphthous Ulcer Healing with Low Dose Prednisolone Bilayer Mucoadhesive Buccal Film.

BACKGROUND: Recurrent aphthous ulcer (RAU) is one of the most common ulcerative diseases of the oral mucosa which is recurrent, painful and slow to heal. Treatment is primarily for pain relief and promotion of healing to shorten the disease duration or reduce the rate of recurrence. OBJECTIVE: Development of a new design of topical buccal bilayer mucoadhesive films containing sodium alginate and gellan gum loaded with low dose of 1 mg prednisolone sodium phosphate to reduce the treatment period and decrease side effects of systemic treatment. METHODS: Films were prepared by solvent casting technique and evaluated to ensure optimum film characteristics, and in vivo efficiency. RESULTS: The bilayer films were thin, flexible with good water uptake, mucoadhesive and mechanical properties. In vitro drug release was sustained and showed anomalous non-Fickian kinetics. SEM confirmed the development of bilayer formation. Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetery indicated no chemical interaction between the layers. In vivo study in rabbits with induced oral ulceration showed complete ulcer healing within 4-5 days by once daily treatment of the studied film. Histological examination indicated no inflammation on treatment sites compared to inflamed tissue on the control sites. CONCLUSION: The results suggested that buccal application of the developed bilayer mucoadhesive films loaded with only 1mg of prednisolone provided mucoadhesive and convenient application and was able to promote RAU healing with shorter treatment duration.

EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be effective and safe in the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide everolimus access to patients with SEGA associated with TSC and to mainly assess the safety and also efficacy of everolimus in a real-world setting. METHODS: EFFECTS was a phase 3b, open-label, noncomparative, multicenter, expanded access study. Eligible patients were ≥ 3 years of age, with a definite diagnosis of TSC, and with at least one SEGA lesion identified by MRI or CT scan. Patients received once daily everolimus (dose adjusted to attain a trough level of 5-15 ng/mL). Safety evaluation was the primary objective and included collection of adverse events (AEs) and serious AEs, with their severity and relationship to everolimus. Efficacy evaluation, which was the secondary objective, was based on the best overall response as per medical judgment. RESULTS: Of the 120 patients enrolled, 100 (83.3%) completed the study. Median age of patients was 11 years (range, 1-47). Median daily dose of everolimus was 5.82 mg (range, 2.0-11.8). Median duration of exposure was 56.5 weeks (range, 0.3-130). The overall incidence of AEs was 74.2%. Aphthous stomatitis (18 [15.0%]), pyrexia (18 [15.0%]), bronchitis (11 [9.2%]), and stomatitis (10 [8.3%]) were the most common AEs reported. Overall, 25 patients had grade 3 AEs; most frequent was stomatitis (4 [3.3%]). Grade 4 AEs were reported in three (2.5%) patients. A total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%) were of grade 3 or 4. In eight (6.7%) patients, AEs led to drug discontinuation. With regard to efficacy, 81 (67.5%) patients had a partial response, 35 (29.2%) had a stable disease, and one (0.8%) had progressive disease. The response was unknown in three (2.5%) patients. CONCLUSION: This study confirms the acceptable safety profile of everolimus in patients with SEGA associated with TSC in a real-world setting. The results further support the efficacy of everolimus in the treatment of SEGA associated with TSC. (EudraCT: 2010-022583-13).

Cutaneous adverse reactions of imatinib therapy in patients with chronic myeloid leukemia: A six-year follow up.

Imatinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Cutaneous adverse reactions of imatinib therapy have been reported in 7%-88.9% patients. We sought to evaluate the prevalence rates of cutaneous adverse reactions of imatinib therapy and to investigate the clinical and pathological characteristics of these reactions. Sixty-six patients (36 men, 30 women; age range 19-83 years) with CML treated with imatinib between 2008 and 2014 were included in the study. Clinical and pathological features of the adverse reactions were investigated. Cutaneous adverse reactions were the most common adverse effects of imatinib therapy and were seen in nine patients with a prevalence rate of 13.6%. The second most common adverse effect was musculoskeletal pain (12.1%). The following cutaneous reactions were observed in patients: edema, rash, pigmentary changes, aphthous stomatitis, alopecia, cutaneous dryness, hyperhidrosis and cheilitis. Imatinib therapy was discontinued in four patients because of various adverse effects. Although the prevalence rate of cutaneous adverse reactions in our study was lower than that in several other studies, cutaneous reactions were common in our study. The relatively low prevalence rate of adverse reactions may be related to the low dosage of imatinib (400 mg/day) used to treat our patients and may have been affected by pharmacogenetic characteristics of our population.

Paradoxical mucocutaneous flare in a case of Behçet's disease treated with tocilizumab.

We report on a patient with a long-standing history of recurrent oral aphthosis and pseudofolliculitis, diagnosed with Behçet's disease (BD), previously treated with high-dose prednisone, colchicine, cyclosporine, cyclophosphamide and methotrexate, all of which were partially effective. Treatment with the chimeric mouse-human anti-tumour necrosis factor (TNF)-α monoclonal antibody infliximab brought about the resolution of mucocutaneous lesions for a period of 6 years. After an oral and articular BD relapse, the anti-interleukin-6 agent tocilizumab was started in association with high-dose prednisone. Unexpectedly, the patient experienced a paradoxical mucocutaneous flare following tocilizumab administration, which worsened after the second infusion. Tocilizumab was then discontinued, and total recovery was achieved after the patient was started on the fully human anti-TNF-α monoclonal antibody golimumab in association with colchicine and methylprednisolone.

[Response to everolimus in patients with giant cell astrocytoma associated to tuberous sclerosis complex]. / Respuesta a everolimus en pacientes con astrocitoma de celulas gigantes asociado al complejo esclerosis tuberosa.

INTRODUCTION: Subependymal giant cell astrocytomas (SEGA) appear in 5-20% of patients with tuberous sclerosis complex (TSC) and are the most common brain tumours in TSC. They are benign tumours, of a glioneural stock, that develop mainly in the first two decades of life, generally close to the foramen of Monro, and can trigger hydrocephalus and intracranial hypertension. It is one of the leading causes of death in TSC. Recently mTOR inhibitors have proved to be a therapeutic alternative to surgical excision. AIM. To describe our experience of using everolimus to treat patients with SEGA and TSC. PATIENTS AND METHODS: We conducted a prospective study of the responses of patients with TSC and at least one SEGA undergoing growth. RESULTS: Three females and three males with a mean age of 12.3 years received treatment. One patient had previously undergone surgery due to SEGA with hydrocephalus. The maximum mean diameter of the SEGA on beginning treatment was 15.3 mm (range: 11.3-24.8 mm). Treatment was established with everolimus, 2.5 mg/day administered orally in patients with a body surface area < 1.2 m2, and 5 mg/day in patients with a body surface area > 1.2 m2. Two patients presented hypertriglyceridemia; one, anorexia; another, a mouth ulcer; and one, amenorrhoea. The mean reduction in the volume of the SEGA at three months of treatment was 46%, and the reduction remained steady in later control examinations (6-25 months). CONCLUSIONS: Treatment with everolimus reduces the size of SEGA associated with TSC with an adequate safety profile, and constitutes an alternative to surgery in certain cases.

TITLE: Respuesta a everolimus en pacientes con astrocitoma de celulas gigantes asociado al complejo esclerosis tuberosa.Introduccion. Los astrocitomas subependimarios de celulas gigantes (SEGA) se presentan en el 5-20% de los pacientes con complejo esclerosis tuberosa (CET) y son los tumores cerebrales mas comunes en el CET. Son tumores benignos, de estirpe glioneural, que se desarrollan fundamentalmente en las primeras dos decadas de la vida, en general cercanos al foramen de Monro, y pueden ocasionar hidrocefalia e hipertension intracraneal. Constituyen la principal causa de muerte en el CET. Recientemente, los inhibidores mTOR han demostrado ser una alternativa terapeutica a la reseccion quirurgica. Objetivo. Describir nuestra experiencia con everolimus para el tratamiento de pacientes con SEGA y CET. Pacientes y metodos. Estudio prospectivo de la respuesta de los pacientes con CET y al menos un SEGA en crecimiento. Resultados. Recibieron tratamiento tres mujeres y tres varones con una edad media de 12,3 años. Un paciente habia sido previamente intervenido quirurgicamente por SEGA con hidrocefalia. El diametro maximo medio del SEGA al inicio del tratamiento era de 15,3 mm (rango: 11,3-24,8 mm). Se inicio tratamiento con everolimus, 2,5 mg/dia por via oral en pacientes con superficie corporal < 1,2 m2 y 5 mg/dia en pacientes con superficie corporal > 1,2 m2. Dos pacientes presentaron hipertrigliceridemia; uno, anorexia; otro, un afta; y una paciente, amenorrea. La reduccion media del volumen del SEGA a los tres meses de tratamiento fue del 46%, y la reduccion se mantuvo estable en controles posteriores (6-25 meses). Conclusiones. El tratamiento con everolimus disminuye el tamaño de los SEGA asociados a CET con un perfil de seguridad adecuado, y constituye una alternativa a la cirugia en casos seleccionados.

[Oral toxicity of targeted anticancer therapies]. / Toxicité endobuccale des thérapies ciblées anticancéreuses.

While toxicity of targeted anticancer therapies on the oral mucosa seems relatively frequent in clinical practice, it has not been properly characterized to date, apart from aphthous-like lesions due to mTOR inhibitors. Herein, we report the main oral lesions associated with these new therapies, with a description of the most frequent but also the most characteristic clinical manifestations of these drugs, such as anti-EGFR-induced mucositis, BRAF-inhibitor-associated hyperkeratosis, benign migratory glossitis and osteonecrosis of the jaw observed with angiogenesis inhibitors, as well as lesions more specifically linked with imatinib.

Mammalian target of rapamycin inhibitor-associated stomatitis.

With the recent introduction of inhibitors of mammalian target of rapamycin (mTOR) in oncology, distinct cutaneous and oral adverse events have been identified. In fact, stomatitis and rash are documented as the most frequent and potentially dose-limiting side effects. Clinically, mTOR inhibitor-associated stomatitis (mIAS) more closely resembles aphthous stomatitis than oral mucositis due to conventional anticancer therapies. While most cases of mIAS are mild to moderate and self-limiting, more severe and persistent mIAS can become a dose-limiting toxicity. Small ulcerations may cause significant pain and mucosal sensitivity may occur in the absence of clinical changes. Use of clinical assessment tools that are primarily driven by ulceration size may underestimate mIAS, and assessment should include patient-reported outcomes. This article provides an up-to-date review of the clinical presentation, terminology, pathogenesis, assessment and management of mIAS and other mTOR inhibitor-associated oral adverse events. In addition, areas of future research are considered.