Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management

Mucocutaneous blistering autoimmune diseases are a group of systemic, rare, chronic disorders characterized by humoral-mediated immunologic mechanisms against epithelial, basement membrane, and subepithelial tissues. Morbidity and mortality can be completely different among these diseases, with outcome being dependent on an early and accurate diagnosis, systemic comorbidities, and the patient's response to treatment. Definitive diagnosis is based on clinical and histopathologic findings. Because clinical presentations among these diseases are often similar, different immunofluorescence tests and ELISAs are used to confirm the specific diagnosis. Oral mucosa may often be the first site of clinical manifestation from which the disease spreads to other mucosal surfaces and skin. Thus, often dentists and oral medicine specialists may be the first to encounter patients with such diseases. In this review we discuss the most frequent autoimmune vesicobullous disorders, namely pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA disease

When orofacial pain needs a heart repair

Objectives: The association of chronic orofacial pain (COFP) and congenital heart disease has never previously been reported. We report the first case of COFP secondary to a right-to-left shunt (RLS) due to asymptomatic patent foramen ovale (PFO) in a patient with prothrombotic states. Materials and methods: A 48-year-old female patient presented with a 10-month history of left-sided facial pain who was initially diagnosed with persistent idiopathic facial pain (PIFP) on account of its similar characteristics. Magnetic resonance imaging (MRI) of the brain revealed gliosis and carotid siphon tortuosity; in addition, hyperhomocysteinaemia due to the homozygosis mutation for 5,10 MethyleneTetraHydroFolate Reductase was identified. Transcranial doppler ultrasonography was requested from a neurology consultant which revealed a high degree of RLS. Subsequently, a cardiological evaluation was performed; the specialist requested a transesophageal echocardiography that detected an interatrial septum aneurysm with PFO. Results: Based on the analysis of the patient's high degree of RLS, prothrombotic state and gliosis in relation to age, the cardiological consultant chose to perform a percutaneous closure of the PFO to avoid the risk of a cryptogenic stroke. After PFO closure, a complete remission of the pain was obtained. Conclusions: The disappearance of the pain supports the possible association between RLS and COFP. PFO with RLS has been suggested as a risk factor for cryptogenic stroke, especially in association with other thromboembolic risk factors. Therefore, the early detection, in this case, could be considered a possible lifesaver. Communication between different care providers is essential when the patient presents symptoms of facial pain which are of an atypical nature

Autoimmune mucocutaneous blistering diseases after SARS-Cov-2 vaccination: A Case report of Pemphigus Vulgaris and a literature review

Background: Cases of severe autoimmune blistering diseases (AIBDs) have recently been reported in association with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Aims: To describe a report of oropharyngeal Pemphigus Vulgaris (OPV) triggered by the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/ BioNTech) and to analyze the clinical and immunological characteristics of the AIBDs cases reported following the SARS-CoV-2 vaccination. Methods: The clinical and immunological features of our case of OPV were documented. A review of the literature was conducted and only cases of AIBDs arising after the SARS-CoV-2 vaccination were included. Case report: A 60-year old female patients developed oropharyngeal and nasal bullous lesions seven days after the administration of a second dose of the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/BioNtech). According to the histology and direct immunofluorescence findings showing the presence of supra-basal blister and intercellular staining of IgG antibodies and the presence of a high level of anti-Dsg-3 antibodies (80 U/ml; normal < 7 U/ml) in the serum of the patients, a diagnosis of oropharyngeal Pemphigus Vulgaris was made. Review: A total of 35 AIBDs cases triggered by the SARS-CoV-2 vaccination were found (including our report). 26 (74.3%) were diagnosed as Bullous Pemphigoid, 2 (5.7%) as Linear IgA Bullous Dermatosis, 6 (17.1%) as Pemphigus Vulgaris and 1 (2.9%) as Pemphigus Foliaceus. The mean age of the sample was 72.8 years and there was a predominance of males over females (F:M=1:1.7). In 22 (62.9%) cases, the disease developed after Pfizer vaccine administration, 6 (17.1%) after Moderna, 3 (8.6%) after AstraZeneca, 3 (8.6%) after CoronaVac (one was not specified). All patients were treated with topical and/or systemic corticosteroids, with or without the addition of immunosuppressive drugs, with a good clinical response in every case. Conclusion: Clinicians should be aware of the potential, though rare, occurrence of AIBDs as a possible adverse event after the SARS-CoV-2 vaccination. However, notwithstanding, they should encourage their patients to obtain the vaccination in order to assist the public health systems to overcome the COVID-19 pandemic

Aseptic Meningitis in Oral Medicine: Exploring the Key Elements for a Challenging Diagnosis: A Review of the Literature and Two Case Reports

Aseptic meningitis (AM) is a potentially severe and life-threatening disease characterized by meningeal inflammation, usually with mononuclear pleocytosis. It represents a challenging and controversial issue in medicine for multiple etiologies, classification, and difficult diagnosis in the face of nonspecific sets of signs and symptoms. In the area of interest of oral medicine, in specific clusters of patients, even if rare, the occurrence of aseptic meningitis can pose a diagnostic and management dilemma in the following potential etiologies: (i) systemic diseases with oral and meningeal involvement, which include Behçet’s disease and Sjögren syndrome; (ii) drug-induced aseptic meningitis; (iii) aseptic viral meningitis, mostly related to herpes simplex virus infection and hand, foot, and mouth disease, caused by enteroviruses. In this review, clinical manifestations, diagnostic methodologies, incidence, treatment, and prognosis for each of these clinical entities are provided. Furthermore, two illustrative case reports are described: a patient suffering from recurrent oral ulcers, in which a sudden onset of AM allows us to diagnose Neuro Behçet’s disease, and a patient affected by pemphigus vulgaris, manifesting a drug-induced AM. Exploring this complex clinical entity scenario, it is clear that an oral medicine specialist has a place on any multidisciplinary team in making such a challenging diagnosis

Oral dysplastic complications after HSCT: Single case series of multidisciplinary evaluation of 80 patients

Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem‐cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft‐versus‐host disease (cGVHD). The aim of this study was to describe a cohort of post‐HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time. In this retrospective cohort study, we present a cohort of hematological patients that underwent HSCT. Demographic variables, clinical hematological data, data regarding acute graft‐versus‐host disease (aGVHD) and cGVHD, and oral clinical features were analyzed. We focused on clinicopathological features of a subgroup of 22 patients with oral cGVHD and OSCC after HSCT. Among 80 included patients, 46 patients (57,5%) developed aGVHD and 39 patients (48,7%) developed cGVHD. Oral mucosa was involved in 17 patients with aGVHD (36,9%) and in 22 patients (56,4%) with cGVHD. Out of a total of 22 oral biopsies, roughly 40% revealed mild to moderate dysplasia, and 32 % were OSCC. In the absence of international agreement on the best timing of oral follow‐up after HSCT, it is mandatory to establish a close multidisciplinary evaluation in order to prevent the onset of HSCT-related OSCC and to reduce post‐transplant mortality due to secondary tumors

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). Materials and Methods: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). Results: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group −0.1% [−0.5%−0.3%] vs. control group −0.1% [−0.4%−0.2%]; p =.482). Also, no difference was found in ΔBMI (p =.316) or ΔGlucose (p =.538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p =.041 for the trend among PGWBS tertiles) and BMI (p =.022). Conclusions: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended

Devices for less invasive surfactant therapy: a manikin study

peer reviewedBackground: “Less invasive surfactant therapy” (LIST), or tracheal instillation of surfactant through a small catheter in spontaneously breathing infants, is gaining popularity. Different catheters are currently used for this purpose: a nasogastric tube inserted with (LISA) or without (Take Care) Magill’s forceps, a 13 cm 16G adult angiocath (MIST), a 30 cm F4 angiography catheter (Stockholm). We developed a specific device by combining a F5 umbilical catheter and an intubation stylet (Liege). We aimed to compare those 5 devices using INSURE as a reference. Methods: 20 neonatologists from 4 institutions supporting different surfactant instillation policies intubated 2 manikin heads with the 5 catheters and an endotracheal tube in a predetermined random sequence. Water was flushed trough the catheter. Video review provided times between laryngoscope (T1) or catheter insertion (T2) in the mouth and water flowing from the trachea. Participants gave an ease of use score (range: 1-9) for each catheter. Results: Procedural times were longer with the Take Care method and shorter with the Liège device (Table). Failure rates were higher for LIST procedures than for INSURE. Take Care and LISA were rated as more difficult, while Liège, Stockholm and INSURE were considered easier. Conclusions: LIST procedures remain difficult, even on a manikin. The choice of catheter is important. A device combining the rigidity of a stylet with the soft distal end of an umbilical catheter is associated with procedures of shorter duration and is considered easier by neonatologists

Pharmacokinetics and pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in mice and non-human primates

Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer

Clinical features of patients with type 2 diabetes with and without Covid-19: a case control study (CoViDiab I)

Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. Results: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59–3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42–9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18–8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13–0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12–0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16–0.93, p = 0.033) were found among cases. Conclusions: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes