Melkersson–Rosenthal syndrome in the context of sarcoidosis: a case report

Background Melkersson–Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn’s disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. Case presentation We here present a case of a 59-year-old White woman suffering from Melkersson–Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. Conclusions We propose clofazimine as an alternative treatment in steroid-refractory cases.

Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid

Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.

An anatomical perspective on clinicopathological characteristics and treatment outcomes of dorsal and ventrolateral tongue leukoplakia after carbon dioxide laser surgery

Background The tongue has been identified as a high-risk site for malignant transformation of oral leukoplakia. The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of the dorsal and ventrolateral tongue leukoplakia. Methods Demographic data and pathological results of patients who underwent carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. Results Of the 111 patients enrolled, 80 were males and 31 females, with a mean age of 51.86 ± 11.84 years. The follow-up time was 3.74 ± 4.19 years. Fifteen patients had a postoperative recurrence (13.51%). Four (3.6%) patients developed malignant transformation. Annual transformation rate was 1.08%. There were no differences in the time to develop carcinoma (3.19 ± 1.94 vs. 3.51 ± 2.12 years, P = 0.83), overall cumulative malignant transformation rates (7.41% vs. 2.25%, P = 0.12), and annual transformation rates (2.32% vs. 0.64%, P = 0.099). The prevalence of the ventrolateral tongue leukoplakia was higher than that of the dorsal tongue leukoplakia (P < 0.001). The results of multivariate logistic regression analysis showed that the degree of pathology was the only independent prognostic factor related to postoperative malignant transformation (P = 0.045). Conclusions Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response of the dorsal tongue and ventrolateral tongue leukoplakia to laser therapy of are comparable in postoperative recurrence and postoperative malignant transformation. Clinicians should take a more aggressive attitude toward oral tongue leukoplakia with higher grade of dysplasia.

Treatment of tongue telangiectasia in a patient with hereditary haemorrhagic telangiectasia

A 61-year-old Caucasian woman presented to an outpatient otolaryngology clinic with increased bleeding from a dorsal tongue telangiectasia for 3 weeks. Her history was significant for hereditary haemorrhagic telangiectasia (HHT), a rare condition that causes vascular dysplasia, and recent symptomatic anaemia requiring blood transfusions. After failing medical management with topical haemostatic agents, she was offered and underwent surgical intervention to remove the tongue telangiectasia with duel therapy potassium titanyl phosphate (KTP) laser coblation and bevacizumab injections. A team of otolaryngologists removed the lesion without complications, and the patient denied bleeding, had minimal pain, and endorsed increased quality of life postoperatively. Tongue telangiectasias can cause life-threatening bleeding in some patients with HHT, and no surgical management guidelines exist to treat them. This case demonstrates the efficacy of KTP laser followed by bevacizumab injections in treating tongue telangiectasias in a patient with HHT.

Locally administered heparin-binding epidermal growth factor-like growth factor reduces radiation-induced oral mucositis in mice

Oral mucositis refers to lesions of the oral mucosa observed in patients with cancer being treated with radiation with or without chemotherapy, and can significantly affect quality of life. There is a large unmet medical need to prevent oral mucositis that can occur with radiation either alone or in combination with chemotherapy. We investigated the efficacy of locally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent epithelial proliferation and migration stimulator of the oral mucosa as a potential therapy to prevent radiation induced oral mucositis. Using a single dose (20 Gy) of radiation to the oral cavity of female C57BL/6 J mice, we evaluated the efficacy of HB-EGF treatment (5 µl of 10 µg/ml) solution. The results show that HB-EGF delivered post radiation, significantly increased the area of epithelial thickness on the tongue (dorsal tongue (42,106 vs 53,493 µm2, p < 0.01), ventral tongue (30,793 vs 39,095 µm2, *p < 0.05)) compared to vehicle control, enhanced new epithelial cell division, and increased the quality and quantity of desmosomes in the oral mucosa measured in the tongue and buccal mucosa. This data provides the proof of concept that local administration of HB-EGF has the potential to be developed as a topical treatment to mitigate oral mucositis following radiation.

How Periodontal Disease and Presence of Nitric Oxide Reducing Oral Bacteria Can Affect Blood Pressure

Nitric oxide (NO), a small gaseous and multifunctional signaling molecule, is involved in the maintenance of metabolic and cardiovascular homeostasis. It is endogenously produced in the vascular endothelium by specific enzymes known as NO synthases (NOSs). Subsequently, NO is readily oxidized to nitrite and nitrate. Nitrite is also derived from exogenous inorganic nitrate (NO3) contained in meat, vegetables, and drinking water, resulting in greater plasma NO2 concentration and major reduction in systemic blood pressure (BP). The recycling process of nitrate and nitrite to NO (nitrate-nitrite-NO pathway), known as the enterosalivary cycle of nitrate, is dependent upon oral commensal nitrate-reducing bacteria of the dorsal tongue. Veillonella, Actinomyces, Haemophilus, and Neisseria are the most copious among the nitrate-reducing bacteria. The use of chlorhexidine mouthwashes and tongue cleaning can mitigate the bacterial nitrate-related BP lowering effects. Imbalances in the oral reducing microbiota have been associated with a decrease of NO, promoting endothelial dysfunction, and increased cardiovascular risk. Although there is a relationship between periodontitis and hypertension (HT), the correlation between nitrate-reducing bacteria and HT has been poorly studied. Restoring the oral flora and NO activity by probiotics may be considered a potential therapeutic strategy to treat HT.

Existence of SARS-CoV-2 Entry Molecules in the Oral Cavity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. Dorsal tongue and gingiva, saliva, and tongue coating samples were examined to determine the presence of these molecules in the oral cavity. Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. Furin was localized mainly in the lower layer of stratified squamous epithelium and detected in the saliva but not tongue coating. ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations. These data showed that essential molecules for SARS-CoV-2 infection were abundant in the oral cavity. However, the database analysis showed that saliva also contains many protease inhibitors. Therefore, although the oral cavity may be the entry route for SARS-CoV-2, other factors including protease inhibitors in the saliva that inhibit viral entry should be considered.

Dorsal tongue versus ventrolateral tongue leukoplakia: An anatomical perspective on clinicopathological characteristics and treatment outcomes

Background Among the risks of malignant transformation of oral leukoplakia, tongue has been identified as a high-risk site. Only little information exists on the clinicopathological characteristics and treatment outcomes specific to leukoplakia of the dorsum of the tongue. The comparison of clinicopathological characteristics of the dorsal tongue and ventrolateral tongue leukoplakia is not available in the literature. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes between dorsal and ventrolateral tongue leukoplakia. Methods The demographic data and pathological results of the patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. Results Of 144 enrolled, there were 108 males and 36 females with a mean age 52.17 ± 11.72. The follow-up time was 4.58 ± 4.53 years. Thirty patients had postoperative recurrence (20.83%). Twelve patients developed malignant transformation (8.33%). Annual transformation rate was 2.28%. In comparison of dorsal and ventrolateral tongue leukoplakia, there were no differences in the time to the development of carcinoma (2.62 ± 1.69 VS 3.98 ± 2.77 years), overall cumulative malignant transformation rates (7.50% VS 7.69%), and annual transformation rates (2.86% VS 1.93%). The prevalence of ventrolateral tongue leukoplakia is higher than the dorsal tongue leukoplakia (P < 0.001) Conclusions Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response to laser therapy of dorsal tongue and ventrolateral tongue leukoplakia are comparable in postoperative recurrence and postoperative malignant transformation.