The "great imitator": IgG4-related disease of the oral cavity. Two case reports and scoping review.

This study aimed to review the lesser-known intraoral manifestations of immunoglobulin G4-related disease (IgG4-RD). In this paper we report an unprecedented case of oral IgG4-RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4-RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow-up duration. Fifty-one cases of oral IgG4-RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4-RD should report clear adherence to the recognized international diagnostic criteria of the disease.

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine.

BACKGROUND: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. METHODS: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. FINDINGS: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). INTERPRETATION: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.

Impact of Smoking Habit on Peri-Implant Indicators following Different Therapies: A Systematic Review.

Peri-implant disease and its treatment is becoming a major concern for clinicians as the number of implants placed each year is rising. Smoking is a common habit, and it is associated with an increased risk of developing peri-implant disease. The role of smoking in the response to peri-implant treatment has never been investigated. Searches were conducted in electronic databases to screen articles published until August 2021. The included studies had at least two groups of patients: peri-implant disease only or peri-implant disease and smoking status. Outcomes of interest included plaque index (PI), probing depth (PD), bleeding on probing (BoP), radiographic crestal bone loss (CBL), and analysis of peri-implant sulcular fluid. Seven hundred and forty-nine articles were found in the databases, only 71 articles potentially qualified. A total of seven studies with a minimum follow-up of six months were included. There is no homogeneity in the diagnosis, smoker definition and treatment proposed. All surgical and non-surgical treatment have statistically significantly different outcomes in smokers and nonsmokers. Recognizing this study's limitations, we conclude that smoking might play a significant role on the outcome of peri-implant disease treatment. None of the proposed treatments appear to be significantly more effective.

Chronic mechanical trauma/irritation and oral carcinoma: A systematic review showing low evidence to support an association.

BACKGROUND: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC). OBJECTIVES: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC. DATA SOURCES: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science. STUDY ELIGIBILITY CRITERIA: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC. RESULTS: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed. CONCLUSIONS: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients.

BACKGROUND: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2. METHODS: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively. FINDINGS: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva. INTERPRETATION: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

Poly D,L-Lactide-Co-Glycolic Acid Grafting Material in Sinus Lift.

The poly D,L-lactide-co-glycolic acid (PLGA) is a copolymer used in many therapeutic devices for its high rates of biodegradability and biocompatibility. The principal aim of the research was to evaluate the new bone formation, after 16 (T1) and 28 weeks (T2), in sheep maxillary sinus lift in vivo model using PLGA.Computerized tomography analysis, X-ray microanalysis, and scanning electron microscope analysis of secondary electrons (SE) and the backscattered electrons (BSE) of the samples were detected.After 28 weeks, the computed tomography analysis showed a 22% increase of UH density in the grafting areas. The X-ray microanalysis of the samples showed calcium and phosphorus increase at T1 and T2 follow-up period and the carbon and oxygen concentration decrease. The SE evaluation showed a rapid superficial resorption of the biomaterials at T1 and a completely bone reorganization of biomaterial at T2. The BSE analysis confirmed the SE data and showed the direct and intimate contact between bone and PLGA with a higher calcification in T2 compared to T1.Certainly, still other experiments and a larger number of samples will be necessary to be analyzed to determine the behavior of the PLGA in the bone regeneration; however, the PLGA used in maxillary sinus lift animal model, seem to promote new bone formation that continues increase at 28 weeks after grafting.

Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria.

Chronic ulcerative stomatitis (CUS) is an immune-mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle-aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non-specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium-specific antinuclear antibodies (SES-ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ∆Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.

A Giant-Cell Lesion with Cellular Cannibalism in the Mandible: Case Report and Review of Brown Tumors in Hyperparathyroidism.

A small radiolucent area in the mandible was discovered in a 58-year-old woman with no oral complaints. The patient's history included only hypertension. The lesion was considered as an inflammatory cyst and was enucleated. Three months later, a CT revealed the presence of a cyst-like lesion in the mandible with thin expanded buccal cortical plate, localized erosion, and a polylobate appearance on the lingual aspect of the cortical plate. The histological diagnosis of the lesion was central giant-cell granuloma (CGCG). The lesion was thoroughly enucleated. Nevertheless, another X-ray carried out six months later revealed multiple bilateral osteolytic areas throughout the jaw. In addition, widespread cortical plate erosion was observed, as well as signs of root resorption and periodontal enlargement. There was no sign of neurological involvement, although the nerves appeared to be dislocated. After full blood chemistry analysis and detailed collection of radiographs, the final diagnosis was brown tumors in primary hyperparathyroidism. This case report demonstrates how dental clinicians may be the first-line specialists who identify a complex systemic disease before other clinicians. Finally, it highlights the role of cellular cannibalism in predicting the clinical aggressiveness of brown tumors as well as in other giant-cell lesions.

[Burning oral sensation: when is really BMS?]. / Az égo száj szindrómáról. Diagnózis és etiológia.

The aims and purposes of this systematic review of the international literature are to discuss and clarify some considerations on Burning Mouth Syndrome (BMS). Over the last 40 years, many researchers have addressed this disease clinically or experimentally. Thus, the etiology and pathogenesis of BMS remain unclear. We analyzed the etiopathogenesis of Burning Mouth Syndrome and of the burning oral sensation and currently, we could not find a consensus on the diagnosis and classification of BMS. Further studies are required to better understand the pathogenesis of BMS, and a "Gold Standard" classification is required because not every burning sensation in the mouth is BMS.

An unusual green macular lesion of the gingiva: a foreign-body granulomatous reaction.

The current clinical case highlights the diagnostic process in characterizing an unusual green macular lesion of the maxillary gingiva. A review of the history revealed that the patient had suffered trauma to the oral tissues during a soccer match 2 years prior. An incisional biopsy was performed and microscopic analysis demonstrated the presence of a granulomatous reaction to a needle-shaped, birefringent foreign material. Comparative analysis of a specimen collected from the soccer field confirmed that the foreign material was artificial grass. Foreign material was also found inside the gingival epithelial cells.

Maxillary sinus augmentation with adult mesenchymal stem cells: a review of the current literature.

PURPOSE: Mesenchymal stem cells (MSCs) have been applied in maxillary sinus augmentation (MSA) with clinically successful results. The purpose of this article was to evaluate the systematically acquired evidence for the effectiveness of cell-based approaches in MSA with various scaffolds, and to narratively assess evidence from additional articles that report effectiveness of cell-based approaches in MSA. MATERIALS AND METHODS: Electronic database searches were performed. Inclusion criteria were studies of cell-based approaches in MSA with various scaffolds, in humans, with at least 3 to 4 months of follow-up. Meta-analysis was performed for randomized controlled trials (RCTs) with histologic/histomorphometric evaluation. RESULTS: Fifteen studies (4 RCTs) were considered to be eligible for inclusion in the review. The meta-analysis suggested a marginal, nonstatistically significant positive effect of MSCs on the bone regrowth. CONCLUSIONS: A number of studies have demonstrated the potential for cell-based approaches in MSA; further RCTs that clearly demonstrate benefits of cell-based approach are needed.