Vasileios Zisis

Background/Objectives: Bullous pemphigoid (BP) in children is a rare autoimmune subepidermal blistering condition that shows significant clinical variability depending on age. This narrative review summarizes the available literature on the epidemiology, etiology, clinical manifestations, diagnosis, management, outcomes, and future perspectives of pediatric BP. Methods: A search of the PubMed/MEDLINE and Scopus databases from their inception to July 2026 was conducted for English-language articles on BP in patients younger than 18 years old. After record screening and full-text assessment, 55 publications were selected and narratively synthesized. Results: Infants with BP frequently present with acral and palmoplantar blistering, whereas older children and adolescents show more heterogeneous clinical manifestations. BP180 is the principal autoantigen, although antigenic heterogeneity has been reported. Diagnosis requires integration of clinical, histopathological, and immunopathological findings. Linear IgG and/or C3 deposition along the basement membrane zone on direct immunofluorescence (DIF) is an important but non-specific finding. Salt-split skin testing and antigen-specific serology may assist in distinguishing BP from other autoimmune subepidermal blistering diseases. Corticosteroids are the most frequently reported initial treatment, while dapsone and other steroid-sparing agents have been used in selected patients. Intravenous immunoglobulin (IVIG), immunosuppressants, and targeted therapies have primarily been reported in refractory cases, with evidence derived predominantly from case reports and small series. Conclusions: The prognosis reported in the pediatric literature is generally favorable, although there are some reports of resistant or recurrent cases. However, relapse rates in the long-term are not known. There is a need for multicenter prospective trials and standardization of outcomes.

Objectives: To critically evaluate the clinical evidence on patient-, tooth-, biology-, and treatment-related risk factors for endodontic flare-ups and postoperative pain after nonsurgical root canal therapy. Particular emphasis was placed on the issue of inconsistent results due to differences in definitions and methodological issues. Materials and Methods: PubMed and Scopus were searched on 28 June 2026 using specific search strategies within each database that encompassed endodontic therapy, post-treatment pain, risk factors, and pulpal and periapical lesions. The eligible publications consisted of English clinical studies that had been published from 28 June 2006 to 28 June 2026. Title and abstract screening, full-text eligibility assessment, and data extraction were performed by a single reviewer without independent second-reviewer verification. Seventeen eligible reports were included in the revised narrative synthesis, comprising 13 from the original database searches and four identified through supplementary reference screening. Related genetic publications were considered together because of confirmed or suspected overlap in their patient populations. Due to heterogeneity in study populations, outcome definitions, treatment protocols, follow-up periods, and statistical analyses, findings were evaluated through critical appraisal and narrative synthesis. Results: Preoperative pain showed the strongest association with postoperative pain, whereas evidence specifically addressing clinically defined endodontic flare-ups was more limited. Associations for periapical condition, pulpal diagnosis, and the number of appointments were variable among studies. There was insufficient evidence or inconsistency on the role of age, sex, tooth factors, irrigation, instrumentation, and obturation factors. Psychological factors and genetic polymorphisms emerged as potential factors associated with postoperative pain, although their clinical relevance remains uncertain. Differences in outcome definitions, patient populations, treatment protocols, and adjustment for confounding variables may have contributed to discrepancies between studies. Conclusions: Flare-ups and postoperative pain are two different conditions that have some similarities but must be assessed independently of each other. Preoperative pain can be considered one of the main factors related to postoperative pain. However, the relatively small and methodologically heterogeneous evidence base limits firm conclusions regarding individual risk factors, particularly for clinically defined flare-ups. Further outcome-specific investigations are needed. Clinical Relevance: Evaluation of preoperative symptoms and relevant clinical characteristics may support patient counseling and treatment planning. However, there is no valid predictive tool for individual endodontic flare-ups based on the current literature.

Oral cavity and maxillofacial aspergillosis can take one of four clinically different forms: primary invasive aspergillosis of the oral cavity, invasive aspergillosis of the paranasal sinuses with secondary involvement of the oral cavity, chronic granulomatous invasive fungal rhinosinusitis, and non-invasive maxillary sinus fungus ball. The basis of this narrative review was a structured search of PubMed, Scopus, Cochrane CENTRAL and ClinicalTrials.gov databases. Each of the statements will be identified according to whether it is supported by direct evidence on oral or maxillofacial conditions, or whether it is an extrapolation from invasive fungal rhinosinusitis of mixed fungal aetiology or from invasive aspergillosis occurring at other sites. Direct evidence on primary invasive oral aspergillosis is restricted to small case series from a single centre involving 12–16 patients and individual case reports. Violaceous gingival margin and spontaneous pain progressing to a necrotic ulcer should be suspicious in patients with leukaemia and neutropenia; diagnosis relies on histopathology and culture. Local control in the case series was achieved mostly via haematological remission. Pooled mortality rate of about 31% is derived from acute invasive fungal rhinosinusitis of mixed aetiology and does not apply to the disease of the mouth. Antifungal treatment strategy is based on guidelines and clinical trials of invasive aspergillosis and mucormycosis. Liposomal amphotericin B is used until the exclusion of Mucorales, and either voriconazole or isavuconazole after confirmation of Aspergillus infection, in combination with debridement whenever possible. The fungus ball is related to endodontic and other dental procedures in case–control studies and is removed endoscopically without antifungals. There are no registered clinical trials for oral or sinonasal aspergillosis.

Oral and maxillofacial diseases include a variety of developmental abnormalities, inflammatory and immune-mediated conditions, salivary gland disorders, periodontal diseases, benign and malignant tumors, and complications related to dental treatment

Background: Effective management of peri-implant disease relies primarily on mechanical removal of the bacterial biofilm. However, achieving adequate surface decontamination can be challenging due to complex implant-surface morphology and restricted access to deep peri-implant pockets. This has prompted the use of adjunctive antimicrobial agents to complement mechanical therapy and improve therapeutic outcomes. Objective: To investigate whether the adjunctive use of antimicrobial strategies improves clinical, microbiological, and radiographic outcomes in patients with peri-implant mucositis and peri-implantitis. Materials and Methods: A structured narrative review was conducted using PubMed/MEDLINE and Scopus in July 2026. No database filters concerning language, human participants or study design were applied. During the screening process, only randomized controlled clinical trials involving human participants and available as English-language full texts were selected. Eligible interventions included locally or systemically administered antibiotics, antiseptics, antimicrobial drug-delivery systems, antimicrobial photodynamic therapy (aPDT), ozone-based therapies, and microbiome-modulating adjuncts. Conventional laser therapy was not classified as an eligible antimicrobial intervention. The database searches retrieved 462 records, including 252 from PubMed and 210 from Scopus. Following duplicate removal and eligibility assessment, 100 publications representing 93 independent clinical trials were included. Results: adjunctive antimicrobial efficacy was highly variable and appeared to depend on disease severity, debridement strategy, antimicrobial agent, delivery modality, and follow-up period. Repeated or sustained local antimicrobial delivery was associated with modest, short-term benefits in several studies, whereas chlorhexidine (CHX) generally provided limited additional benefit over mechanical therapy. Evidence for systemic antibiotics remained inconsistent and insufficient to support routine use, while aPDT offered potential benefits that varied according to treatment protocol. Ozone therapy, herbal agents, and novel drug-delivery systems yielded encouraging preliminary results, although evidence remains scarce. Moreover, reductions in bleeding and probing depth (PD) did not reliably correspond to superior microbiological outcomes, radiographic bone gain, or complete disease resolution. Conclusions: Mechanical debridement (MD) and effective plaque control remain central to peri-implant disease management. Some adjunctive interventions produced modest short-term improvements in individual studies; however, the available evidence does not demonstrate durable disease control or support routine use. Therapeutic decisions should be tailored to disease severity, patient and implant characteristics, and the balance between potential benefits and antimicrobial-associated risks. Further well-designed and adequately powered randomized controlled trials with extended follow-up periods are needed to establish more definitive recommendations.

Background: N6-methyladenosine (m6A) is the most abundant mRNA internal modification in eukaryotes and regulates inflammatory and regenerative processes. Many studies relate the dysregulation of m6A-related pathways to periodontal inflammation, imbalance in cell homeostasis, impaired tissue regeneration, and remodeling of the alveolar bone. However, the mechanisms of the relationship between the m6A pathway and periodontitis have not been elucidated clearly yet. Objective: The objective of the current narrative review is to integrate the information related to the role of m6A RNA modification in the pathogenesis of periodontitis by focusing on inflammatory signaling, osteoimmune regulation, periodontal cell activity, bone remodeling, and its possible applications as a diagnosis and treatment approach. Methods: A literature search was conducted in PubMed to identify original research studies investigating the role of m6A RNA methylation and its regulators in periodontitis and periodontal tissues/cells. Out of 49 publications reviewed, 34 original research articles fulfilled the predetermined inclusion criteria. Results: The current literature suggests that N6-methyladenosine (m6A) modification is involved in various interconnected biological processes contributing to the development of periodontitis, including inflammatory responses, inflammasome activation and pyroptosis, osteoimmune reactions by macrophages, osteogenic differentiation, osteoclast formation, cellular senescence, and periodontal cells homeostasis. METTL3 has been reported to be the most widely investigated regulator, but its roles are not consistently harmful or beneficial. Depending on the RNA target, cellular environment, and state of inflammation, some of the m6A-associated pathways have been linked to periodontal inflammation and alveolar bone resorption, while others were linked to osteogenesis and regeneration. Several studies have highlighted the possibility of therapeutic interference in pathways leading to the formation of m6A, while human transcriptomic and gingival/salivary studies suggested that m6A could be used as a biomarker. Conclusions: The m6A modification of RNA is an emerging epitranscriptomic effect relating periodontal inflammation, immune responses, cellular differentiation, and bone remodeling. Even though target molecules and signaling pathways have been experimentally identified as points of potential therapeutic interference, the available evidence remains predominantly preclinical. Future work is expected to validate the diagnostic and therapeutic involvement of the m6A modification in periodontitis.

Background: Amelogenesis imperfecta affecting enamel formation is frequently associated with a variety of malocclusions and eruption disturbances. Orthodontic treatment is crucial in comprehensive patient management. Previous studies have shown that orthodontic treatment becomes more challenging in patients with AI as the defective enamel affects the bracket bonding, retention of appliances and treatment mechanics and often needs modified bonding protocols, pre-treatment restorative build-ups, skeletal anchorage and general multidisciplinary management. There is no evidence of the ideal orthodontic treatment yet; available evidence only consists of case reports and small observational studies that address specific aspects with no established consensus. Therefore, this narrative review aimed to critically examine the contemporaneous evidence on orthodontic assessment and treatment planning in AI patients, drawing on studies identified through a structured literature search. Materials and Methods: An electronic search of the literature was conducted in the PubMed, Scopus, and ScienceDirect databases. Out of 640 records that were initially identified, 11 studies met the inclusion criteria for qualitative synthesis. Results: Bonding issues resulting from enamel defects tend to be identified as a significant clinical challenge necessitating modified orthodontic techniques. The included studies demonstrated that by using individualized treatment planning, modified bonding procedures, fixed appliances, expansion procedures, skeletal anchorage and combined orthognathic surgery in some cases within the multidisciplinary treatment approach, there can be successful orthodontic management for these patients. Conclusions: Vital steps such as early diagnosis, careful treatment planning, and coordination with restorative and prosthodontic treatment were associated with better functional and esthetic outcomes. Consequently, even though there is limited evidence, the available literature supports a customized interdisciplinary approach as the most predictable and effective strategy for managing orthodontic problems in patients with AI, while emphasizing that case reports and small observational studies are the main sources of current findings.

Background: Oral potentially malignant disorders (OPMDs) comprise clinically and histologically heterogeneous lesions associated with an increased risk of oral squamous cell carcinoma (OSCC). Histopathological grading of oral epithelial dysplasia (OED) remains central to risk estimation but has limited predictive precision. Podoplanin and selected cancer stem cell (CSC) or stemness-associated markers may capture complementary biological processes involved in progression. Objective: To synthesize evidence on podoplanin and selected CSC or stemness-associated markers as indicators of malignant transformation and risk stratification across a prespecified OPMD spectrum, while distinguishing longitudinal prediction from cross-sectional, diagnostic, and mechanistic evidence. Methods: Three original PubMed searches covered database inception to 13 July 2026. A post hoc recall audit against three key evidence syntheses identified one eligible longitudinal report missed during the initial selection; this report was added by backward citation checking. A broader supplementary sensitivity query was run during revision and reported separately without being merged into the original selection counts. In total, 47 publications were included. Study design, effect measure, threshold provenance, internal validation, and possible cohort overlap were charted and synthesized narratively. Results: Among the biomarkers reviewed, podoplanin had the most developed longitudinal evidence, including a pooled hazard ratio (HR) of 3.72 (95% confidence interval [CI] 2.40–5.76) in one meta-analysis. A separate diagnostic-accuracy synthesis reported sensitivity of 78.9% and specificity of 55.0%, corresponding to a positive likelihood ratio (LR+) of 1.75 and a negative likelihood ratio (LR−) of 0.38. Predictive values varied materially with baseline transformation risk. CD133, BMI1, and ABCG2 showed large associations in individual cohorts, but independent replication and external validation were limited. Cross-sectional expression gradients were not treated as evidence of prospective prediction. Conclusions: Within the defined OPMD scope, podoplanin has the most developed longitudinal evidence, but its predictive values are prevalence-dependent and no marker is sufficiently validated for stand-alone clinical use. Prospective multicenter studies should compare prespecified biomarker models with established clinical, histopathological, and molecular predictors and should evaluate calibration, clinical utility, and external validity before management decisions are altered.

Background: Oral leukoplakia is a clinically important oral potentially malignant disorder with variable risk of progression to oral squamous cell carcinoma. Histopathological grading of oral epithelial dysplasia remains the primary method for risk assessment; however, its predictive accuracy is limited by sampling variability, lesion heterogeneity, and interobserver variation. DNA aneuploidy and abnormal DNA ploidy status have therefore been investigated as objective biomarkers of genomic instability and potential predictors of malignant transformation. Aim: This narrative review evaluates whether DNA aneuploidy or abnormal DNA ploidy status predicts malignant transformation of oral leukoplakia to oral squamous cell carcinoma compared with diploid DNA status, and whether DNA ploidy should be interpreted as a stand-alone prognostic marker or as part of combined risk-assessment models. Materials and Methods: A structured PubMed/MEDLINE search (last performed on 12 July 2026) identified 162 records using terms related to oral leukoplakia, oral potentially malignant disorders, DNA ploidy, DNA aneuploidy, cytometry, malignant transformation, and oral squamous cell carcinoma. After screening and full-text eligibility assessment, 45 studies were included and organised according to their evidential role as core prognostic studies, PVL-specific subgroup evidence, and supporting/background evidence addressing diagnostic relevance, dysplasia correlation, treatment monitoring, genomic instability, and methodological development. Results: Most core prognostic studies showed that DNA aneuploidy, abnormal DNA content, or chromosomal instability was associated with increased malignant transformation risk compared with diploid or non-aneuploid status. Several studies reported higher transformation rates, hazard ratios, or improved prediction when DNA ploidy was combined with dysplasia grading, lesion site, clinical heterogeneity, or other biomarkers. However, predictive performance varied across studies, and DNA ploidy alone often showed modest sensitivity, specificity, or positive predictive value. Diploid or non-aneuploid status appeared more useful for identifying lower-risk lesions, although it did not completely exclude malignant transformation. PVL evidence suggested frequent aneuploidy and aggressive genomic behaviour, but DNA ploidy appeared less reliable for discriminating risk within PVL. Conclusions: DNA aneuploidy and abnormal DNA ploidy status are meaningful markers of genomic instability and are associated with increased malignant transformation risk in oral leukoplakia. However, when used alone, DNA ploidy often shows only modest predictive performance, and prediction improves consistently when it is combined with dysplasia grading and other clinicopathological factors. Their strongest clinical value is therefore as adjunctive biomarkers within combined clinicopathological and molecular risk models, rather than as stand-alone replacements for histopathological assessment; routine clinical implementation is not yet supported by the current evidence.

Background: Pemphigus is a rare group of autoimmune blistering diseases characterized by autoantibody-mediated loss of keratinocyte adhesion, resulting in intraepithelial blister formation involving the skin and mucous membranes. Pemphigus Vulgaris (PV) is the most common type of pemphigus, which usually presents in adulthood and has a prevalence rate of about 2.83 cases per million person years worldwide. The prevalence rate in children and adolescents is relatively uncommon; however, it accounts for about 1.4 to 3.7 percent of all cases of pemphigus vulgaris reported worldwide. The involvement of oral cavity is clinically significant since it can present prior to the disease or as its predominant feature. Hence, this narrative review seeks to review literature on pemphigus with involvement of oral cavity in children and adolescents. Objective: The objective of this study was to review the current literature regarding epidemiology, pathogenesis, clinical presentation, diagnosis, histopathological characteristics, treatment, and outcomes of pemphigus with oral involvement in children and adolescents. Materials and Methods: A literature search was conducted using the PubMed/MEDLINE, Scopus, and Cochrane Library databases to identify relevant studies published between 2015 and 2026. The search strategy included terms related to pemphigus, pediatric patients, and oral manifestations. Articles involving patients younger than 18 years of age with oral involvement were screened according to predefined inclusion criteria. Following database screening, duplicate removal, and full-text assessment, 25 studies comprising a total of 51 patients with documented oral or orofacial involvement were included in the final review. Results: Pemphigus vulgaris was the predominant subtype, with oral lesions representing the initial or sole manifestation in the majority of patients. The gingiva, mucosa, tongue, lip, and palate were the most common affected areas in the mouth. The lesions in these areas usually appeared as painful erosion, ulcers, and desquamative gingivitis. Histopathology with the presence of acantholysis in the suprabasal area and direct immunofluorescence was the most definitive test for diagnosis. Systemic corticosteroids were the mainstay of treatment in conjunction with steroid sparing agents in some cases, with good results in difficult cases using rituximab. Overall, most patients achieved partial or complete clinical remission following appropriate treatment, although relapses were occasionally reported. Conclusions: Pemphigus in children and adolescents is rarely encountered; however, it should be included as a differential diagnosis of erosive/ulcerative lesions. Early identification, diagnosis, and treatment through a collaborative approach from dental practitioners are critical. Further research is required at multiple centers to gain a better understanding of the disease and to develop evidence-based guidelines for diagnosis and treatment of pediatric patients.