Orofacial Manifestation of Systemic Sclerosis: A Cross-Sectional Study and Future Prospects of Oral Capillaroscopy.

BACKGROUND AND OBJECTIVES: oral alterations in Systemic Sclerosis (SSc) patients are widespread and include microstomia, periodontitis, telangiectasias, mandibular resorption, bone lesions, and xerostomia. This cross-sectional study aims to evaluate the differences between SSc patients (cases) and healthy subjects (controls) regarding oral manifestations, quality of life (QoL), and microcirculation alterations. METHODS: plaque index (PCR), periodontal index (PSR), DMFT, salivary flow rate, and buccal opening were measured by expert clinicians. S-HAQ test, the Self-Rating Anxiety State (SAS), the Self-Rating Depression Scale (SDS), and the WHOQOL-BREF test were administered to patients to evaluate their QoL. Microvascular alterations were assessed by oral videocapillaroscopy, performed on gingival and labial mucosa. A statistical analysis was conducted to find significant differences between healthy people and SSc patients. RESULTS: 59 patients were enrolled in this study. Standard salivary flow is significantly more frequent in controls, while xerostomia, reduced flow, microstomia, lip retraction, and periodontitis are significantly more frequent in the cases. Gingival capillaroscopy showed differences concerning loop visibility, thickening of the gum, tortuosity of gingival loops, and reduced gingival density. Labial capillaroscopy demonstrates that visibility of the labial loops, the labial ectasias, and the tortuosity of the loops are significantly associated with the presence of scleroderma. Hand and facial deformities, hypomobility of the tongue, cheeks, lips, microstomia, and xerostomia significantly compromised the quality of life of SSc patients, which was significantly worse among them. Moreover, oral videocapillaroscopy could be a proper diagnostic method to detect oral microcirculation alterations. SSc patients often present ectasias, rarefaction of the reticulum, microhemorrhages, and megacapillaries, which negatively impact their oral health. CONCLUSIONS: periodontitis, reduced salivary flow, and microstomia could be considered SSc oral manifestations. Joint deformities, facial appearance, and comorbidities significantly reduce the QoL of SSc patients compared to healthy subjects. Oral videocapillaroscopy could be an innovative and reliable technique to detect oral microcirculation anomalies.

Could MRONJ Be Related to Osimertinib Monotherapy in Lung Cancer Patients after Denosumab Suspension?

BACKGROUND: Medication-related osteonecrosis of the jaws is the most frequent complication in patients treated or in therapy with antiresorptive/antiangiogenetic drugs. The list of medications possibly related to MRONJ onset is constantly growing; we aimed to report on a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (Osimertinib) as possibly responsible for bilateral maxillary necrosis onset in the herein-described case. METHODS: In June 2023, an oncologic patient with two different maxillary bone exposures was referred to our attention. His medical history revealed a two-year Denosumab regimen along with Osimertinib, the latter not suspended before teeth extractions. The clinicians performed a sequestrum removal and bone debridement after three cycles of antibiotic therapy. RESULTS: Histologic examinations confirmed the clinical diagnosis of MRONJ excluding a metastatic occurrence, while complete mucosal healing was achieved after 15 days. CONCLUSIONS: The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes.

A Comparative Analysis of Post-Retraction Changes in Gingival Height after Conventional and Surgical Gingival Displacement: Rotary Curettage, Diode and Er:YAG Laser Troughing.

The aim of the current article is to analyze and compare post-retraction gingival height changes resulting from six different types of gingival-displacement methods, encompassing both conventional and surgical approaches. The study involved a comparative analysis of 263 teeth (consisting of 128 front teeth, 69 premolars, and 66 molars) from 23 patients. For the investigation, three classic retraction methods were utilized, namely the single-cord technique, retraction paste Expasyl, and retraction paste Astringent. Additionally, three surgical techniques were employed, which included ceramic bur rotary curettage, Er:YAG laser troughing, and diode laser troughing. A randomized split-mouth design was implemented, and a significance level of 0.05 was used for the study. The recovery of the free gingival margin height was assessed on gypsum models that were scanned using an intraoral scanner during the first and second week after the retraction procedure. The results revealed that all retraction methods, except for ceramic bur rotary curettage, led to clinically insignificant levels of gingival recession. The article provides insights into the effectiveness and safety of various gingival-displacement techniques, highlighting that most methods tested in the study resulted in minimal or negligible gingival recession post-retraction.

Targeted Diode Laser Therapy for Oral and Perioral Capillary-Venous Malformation in Pediatric Patients: A Prospective Study.

BACKGROUND: This study describes the management protocol for capillary-venous malformations in pediatric patients and reports the epidemiology of diagnosed and treated cases at the Unit of Odontostomatology of the Aldo Moro University of Bari from 2014 to 2022. METHODS: The authors classified the intraoral and perioral capillary-venous malformations by superficial diameter (<1 cm, 1-3 cm, >3 cm) and ultrasonographical depth extension (≤5 mm, >5 mm). All patients underwent pulsed-mode diode laser transmucosal photocoagulation (8-12 W/cm2); those with malformations that were wide (>3 cm) and deep (>5 mm) received intralesional photocoagulation, too (13 W/cm2). The children received general anesthesia based on their compliance and lesions' extension. The follow-up lasted six months. RESULTS: A total of 22 females and 14 males (age range 4-18 years) presented 63 capillary-venous malformations. Five patients with Sturge-Weber syndrome, seven with hereditary hemorrhagic telangiectasia, and five with angiomatosis showed multiple malformations. The authors found no intraoperative or postoperative complications. Seventeen patients with lesions >1 cm and >5 mm deep required multiple laser sessions to heal. CONCLUSION: The results of the current study support diode laser photocoagulation as the gold standard for the treatment of intraoral and perioral capillary-venous malformations in pediatric patients.

Oral lesions with immunohistochemical evidence of Sars-CoV-2 in swab-negative post-COVID syndrome.

OBJECTIVES: Growing evidence exists about post-COVID condition/syndrome as sequelae of Sars-CoV-2 infection in healed patients, possibly involving the lungs, brain, kidney, cardiovascular and neuromuscular system, as well the persistency of taste dysfunction. Such symptoms develop during or after infection and continue for more than 12 weeks with pathogenesis related to virus persistency but variable by organs or systems. MATERIALS AND METHODS: We recently observed six patients recovered from COVID-19 and with negative RT-PCR testing, showing oral mucosa lesions (mainly ulcers) overlapping those occurring in the acute phase, persisting up to 20 days and thus needing a biopsy with histological investigation and spike protein evaluation by immunohistochemistry. RESULTS: We found epithelial ulceration, inflammatory infiltrate, vessels with increased diameter and flattened endothelium but no thrombi formation; also, we found a weak epithelial SARS-CoV-2 positivity limited to the basal/spinosum layers, progressively decreasing toward the periphery, and the intraepithelial lymphomonocytes, endothelium, and perivascular pericytes too. CONCLUSIONS: Our findings provide evidence that SARS-CoV-2 can persist, as for other organs/systems, also in the oral epithelium/mucosa after the acute phase and can be responsible for lesions, although by a pathogenetic mechanism that should be better defined but certainly referable as the oral mucosa counterpart of post-COVID syndrome.

Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Osteoma of the Jaw as First Clinical Sign of Gardner's Syndrome: The Experience of Two Italian Centers and Review.

Gardner's syndrome (GS) is a combination of polyposis, osteomas, fibromas, and sebaceous cysts. The aim of the study is to highlight whether maxillofacial osteoma could represent an early detection symptom of GS. Patients with suspected osteoma of the jaw underwent genetic and radiographical examinations. The database gathered 19 patients with oral osteoma that was histologically diagnosed; the whole sample was positive for APC gene mutation. Other cranial and peripheral locations were reported. Osteoma of the jaw is a crucial predictive factor of GS, and dentists and oral and maxillofacial surgeons must be aware of the importance of a timely diagnosis.

Clinical Outcomes of Monolithic Zirconia Crowns on Posterior Natural Abutments Performed by Final Year Dental Medicine Students: A Prospective Study with a 5-Year Follow-Up.

The conventional metal-ceramic is still considered the gold standard in fixed prosthetics especially in terms of longevity. Among alternative materials used, Monolithic Zirconia has shown the capability to reconcile excellent biomechanical properties with acceptable aesthetic performance and to overcome several inconveniences related to veneer restorations. This study aims to clinically evaluate Monolithic Zirconia prosthetic crowns on natural abutments in the posterior sectors, performed by final-year dental medicine students (undoubtedly with less experience in the management of such material) by the standardized California Dental Association score system evaluation, to better understand the viability of Monolithic Zirconia. This prospective study was carried out at the Dental School of the University of Bari "Aldo Moro", Italy. Prosthetic rehabilitation included single crowns or a short pontic prosthesis with maximum one intermediate. Final-year dental students performed tooth reduction under the supervision of three expert tutors. The California Dental Association systematics (based on color, surface, anatomical shape, and marginal integrity) were adopted to evaluate the prosthetic maintenance status over time. Annual follow-up visits were re-evaluated by the same parameters each year. Univariate logistic regression analysis was performed to evaluate outcomes and the Kaplan-Meier plot to report survival. The sample consists of 40 crowns performed on 31 patients, 15 males (48.4%) and 16 females (51.6%) with an average age of 59.3 years. The clinical cases subjected to experimental study were found to be "Excellent" (1a/2a/3a/4a) in 34 cases (85%), "Acceptable" in 4 cases (10%), and "To be re-done" in 2 cases (failures) (5%). Our conclusive data support the predictability of Monolithic Zirconia restorations on natural posterior abutments at a long-term follow-up of five years, even when performed by less-experienced clinicians.

Relationship between oral lesions and severe SARS-CoV-2 infection in intensive care unit patients.

OBJECTIVE: Oral lesions received increased attention as likely new signs or secondary manifestations of COVID-19. Therefore, we clinically examined oral cavity of patients with COVID-19 and investigated oral lesions and patient comorbidities as possible risk factors of COVID-19 disease outcome. METHODS: From January to March 2022, a prospective study was conducted by recruiting all COVID-19 patients admitted to the Intensive Care Unit and Respiratory Intensive Care Unit of Maxi-Emergencies Hospital in Bari, Italy. RESULTS: From the enrolled 103 COVID-19 patients, 46.6% were females and 53.4% were males. Findings show that risk of presenting with severe COVID-19 disease was higher in patients who developed oral lesions related to COVID-19 than those with no oral lesions (RR = 7.998, p = .002). Next, patients with concomitant autoimmune diseases were at higher risk of a negative COVID-19 disease outcome than those without comorbidities (OR = 8.838, p = .026). CONCLUSIONS: COVID-19-related lesions of oral mucosa should not be ignored as they can be early and easily detectable signs of severe COVID-19 disease condition, thus, serving as a prevention measure for any potential unfortunate event. Findings of this study, without implying causation, offer a direction for future investigations that aim to confirm the presence of specific oral lesions in COVID-19 patients as signs of severe disease progression.

Medication-related osteonecrosis of the jaw triggered by endodontic failure in oncologic patients.

OBJECTIVES: To describe the association between endodontic treatment failure and medication-related osteonecrosis of the jaw (MRONJ) in a cohort of oncologic patients in therapy with antiresorptive and antiangiogenic drugs. MATERIALS AND METHODS: Patients were selected as affected by MRONJ in absence of the common local risk factors (oral surgical procedures or ill-fitting dentures) but showing failure of previous endodontic treatment performed at least 6 months before the starting of antiresorptive/antiangiogenic therapies. Jaw lesions were all surgically treated and patients underwent a strict clinical and radiological follow-up. RESULTS: Among 18 patients, who developed 18 MRONJ, the only detectable local risk factor was the presence of teeth with failed endodontic treatment (more precisely, root canal underfilling in eight cases, root canal overfilling in two cases, root perforation in three cases, root fracture in five cases). All patients completely healed after surgical procedure and no recurrence was observed. CONCLUSIONS: Endodontic treatment failure should be considered a local risk factor for MRONJ development in oncologic patients. For such reason, it is mandatory to carefully evaluate them prior than the beginning of antiresorptive and antiangiogenic drugs administration.

Recent Advances in 3D Printing of Polymers for Application in Prosthodontics.

Contemporary mass media frequently depict 3D printing as a technology with widespread utilization in the creation of dental prosthetics. This paper endeavors to provide an evidence-based assessment of the current scope of 3D printing's integration within dental laboratories and practices. Its primary objective is to offer a systematic evaluation of the existing applications of 3D-printing technology within the realm of dental prosthetic restorations. Furthermore, this article delves into potential prospects, while also critically examining the sustained relevance of conventional dental laboratory services and manufacturing procedures. The central focus of this article is to expound upon the extent to which 3D printing is presently harnessed for crafting dental prosthetic appliances. By presenting verifiable data and factual insights, this article aspires to elucidate the actual implementation of 3D printing in prosthetic dentistry and its seamless integration into dental practices. The aim of this narrative review is twofold: firstly, to provide an informed and unbiased evaluation of the role that 3D printing currently plays within dental laboratories and practices; and secondly, to instigate contemplation on the transformative potential of this technology, both in terms of its contemporary impact and its future implications, while maintaining a balanced consideration of traditional dental approaches.

The New Era of Salivaomics in Dentistry: Frontiers and Facts in the Early Diagnosis and Prevention of Oral Diseases and Cancer.

Nowadays, with the development of new and highly sensitive, blood is not the only medium of choice for the diagnosis of several diseases and pathological conditions. Saliva is now considered a safe and non-invasive sample to study oral and systemic diseases, showing great diagnostic potential. According to several recent studies, saliva has emerged as an emerging biofluid for the early diagnosis of several diseases, indicated as a mirror of oral and systemic health and a valuable source of clinically relevant information. Indeed, several studies have observed that saliva is useful for detecting and diagnosing malignant tumours, human immunodeficiency virus, heart disease, and autoimmune diseases. The growing realisation that saliva is an inexhaustible source of information has led to the coining of the term 'Salivaomics', which includes five "omics" in connection with the main constituents of saliva: genome and epigenome, transcriptomics, metabolomics, lipidomics, proteomics and microbiota. All those may be changed by disease state, so they offer significant advantages in the early diagnosis and prognosis of oral diseases. The aim of the present review isto update and highlight the new frontiers of salivaomics in diagnosing and managing oral disorders, such as periodontitis, premalignant disorders, and oral squamous cell carcinoma (OSCC).

Calcification of the Atlanto-Occipital Ligament (Ponticulus Posticus) in Orthodontic Patients: A Retrospective Study.

BACKGROUND: Ponticlus Posticus (PP) is a rare anomaly of the first cervical vertebra easily identifiable in lateral cephalometric radiograph and typically required for orthodontic diagnosis. The aim of this study is to evaluate the PP prevalence in lateral Cephalograms in a cohort of orthodontic patients treated at the Dental School of the University of Bari 'Aldo Moro', Italy, and to find possible connection between PP and other dental anomalies, as well as the patient's cephalometric characteristics. METHODS: A total of 150 panoramic radiographs and 150 lateral Cephalograms, obtained for orthodontic use only, were evaluated. No patients were referred to for congenital syndromes or disease, or a history of previously occurred maxillofacial trauma. A detailed cephalometric study was performed for each patient, and the whole cohort was divided according to the common three dental malocclusion classes. The values obtained were analyzed using the Chi-Square Test. RESULTS: PP prevalence was 8% (12 of 150 cases), where the complete and partial forms observed 4.7% and 3.3%, respectively. Although females were more affected (9.6%), no statistically significant sex-related difference was found. Furthermore, no statistically significant relationship regarding age or dental anomalies (dental agenesis/palatal impacted canines) among the groups was observed either. Cephalometric analyses revealed that half of the subjects with PP were sagittal skeletal class I and had vertical hyper-divergence. CONCLUSIONS: PP is a frequent anatomical variation of the cervical vertebra, apparently unrelated to the skeletal malocclusion type or dental anomalies. The current study needs to further confirm the congenital hypothesis of PP's origin already reported in literature.

Laser-Assisted Gingivectomy to Treat Gummy Smile.

Excessive gingival display (EGD) is the extensive exposure of the gingiva during a smile. It is a common concern among patients, which may compromise the esthetic outcome of the dental treatment. Dental lasers demonstrate several advantages for soft tissue dental surgery compared with conventional surgical methods related to their technical characteristics. Owing to the excellent coagulation, especially of the surgical lasers, reduced to no need of anesthesia or suturing and faster healing, they demonstrate optimal clinical results. Nevertheless, good knowledge of laser-tissue interaction is required to obtain the best predictable results without gingival recession or bone tissue damage.

Peri-Implant Metastasis as First Manifestation of an Unknown Lung Cancer: Literature Review and Two New Cases.

Metastases around dental implants are extremely rare. They usually represent a secondary localization of a multiorgan metastatic neoplasm but also are, exceptionally, recognized as the first clinical manifestation of a still unknown cancer of whatever organ. Metastases usually manifest as rapidly growing lesions of hard and soft tissues and always represent a true diagnostic/therapeutic dilemma both for clinicians in choosing the more appropriate treatment and for pathologists in recognizing the primary tumor when still undiagnosed. We report 2 distinct cases of metastasis occurring around dental implants in the maxilla and mimicking peri-implantitis at the onset; more precisely, in one case, the lesion involved exclusively the alveolar bone, where an implant were previously inserted, while in the other case, a neoplasm caused bone destruction around the fixture with an impressive and rapid exophytic growth. In both cases, maxillary lesions were the first metastatic manifestation of an unknown adenocarcinoma of the lung.

The Effect of the Tumor Microenvironment on Lymphoid Neoplasms Derived from B Cells.

Lymphomas are characteristic tumors surrounded by an inflammatory microenvironment. The cells of the microenvironment are essential for the growth and survival of neoplastic cells and are recruited through the effect of cytokines/chemokines. Lymphomas include heterogeneous groups of neoplasms infiltrating various lymphoid structures which may arise from B lymphocytes, T lymphocytes, and natural killer (NK) cells at various stages of their differentiation state. In this review article, we analyze the literature data concerning the involvement of the tumor microenvironment (TME) in the progression of lymphomas and the recent advances in the analysis of microenvironment components in the most common forms: some mature B cell lymphoma neoplasms and classic Hodgkin lymphomas. The complex crosstalk between the TME and tumor cells led to the discovery of many mechanisms usable as molecular-targeted therapy through the control of diverse elements of the TME, varying from inhibitors of angiogenic cytokines and their receptors to the regulation of cells' activities and the novel immune checkpoint inhibitors.

Cranio-Mandibular Disorders after Whiplash Injury: A Mono-Institutional Clinical Study on 31 Patients.

BACKGROUND: Whiplash is a consequence of traumatic injuries, mostly related to road accidents, with variable clinical manifestations, also known as Whiplash Associated Disorders, such as neck, head and temporo-cranio-mandibular pain. METHODS: The current study aims to evaluate the onset and evolution of temporomandibular joint pain in people with whiplash in a study group treated with the use of Zimmer Collars (adjustable rigid cervical collars for neck immobilization), as compared to a control group. This prospective study included 31 patients followed by the Dental Prosthesis Department of the University of Bari "Aldo Moro": 20 patients with whiplash (age range: 20-39 years) treated with Zimmer collars and 11 patients with whiplash (age range: 20-33 years) who were not. Immediately after the whiplash occurred, a visual analogue scale (VAS) was used to describe the intensity of pain and to complete the chart of the European Academy of Craniomandibular Disorders. Five out of twenty patients, already treated with a Zimmer collar, wore an occlusal splint as well because of persistent pain reported at the 28-day and 60-day follow-up and were supported by pharmacological therapy with analgesics (paracetamol) and muscle relaxants (thiocolchicoside). RESULTS: During the last follow-up (at six months), three out of five patients displayed a residual VAS score of 3, 4, and 5, respectively, while the remaining two displayed a VAS of 0. In the control group, four out of eleven patients needed to wear an occlusal splint but without muscle relaxants and analgesics pharmacological therapy; these four corresponded to the patients showing a residual painful symptomatology, with VAS reaching value of 2, and also were the oldest patients of the group. Data regarding VAS values and Zimmer collar use, both at the first visit and six months later, were statistically analyzed. CONCLUSION: Our prospective study highlights how whiplash-associated acute disorders are often self-limiting over a period of few months, thus reducing the possibility of symptom chronicity; the latter seems to be strictly related to lesion severity, pre-existence of a craniomandibular dysfunction and patient age, but appears to be independent from Zimmer collar use, as statistically confirmed.

Peri-implantitis-like medication-related osteonecrosis of the jaw: Clinical considerations and histological evaluation with confocal laser scanning microscope.

OBJECTIVE: In the recent years, an increasing number of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) have been reported in literature, both in oncologic and osteoporotic patients. The aim of this study is to describe 19 cases of patients previously diagnosed as affected by peri-implantitis, who were treated for PI-MRONJ, with consideration on clinical and histopathological features. MATERIALS AND METHODS: Patients included were affected by postmenopausal osteoporosis and were administered with different antiresorptive drugs. Due to the presence of clinical and radiological signs of peri-implantitis not healed after non-surgical periodontal treatment, they were referred to the Complex Operating Unit of Odontostomatology of the University of Bari. Then, after a drug holiday of at least 3 months and cycles of antibiotics, and after other cycles of periodontal treatment, patients underwent the surgical removal of implant fixtures and surrounding bone. RESULTS: Although the previous diagnosis of peri-implantitis, the histopathological analysis with both conventional and confocal laser scanner microscopy confirmed the diagnosis of peri-implantitis-like MRONJ. CONCLUSION: Peri-implantitis not healed after conventional treatment in patients at risk on MRONJ occurrence should be considered as peri-implantitis-like PI-MRONJ and treated as required in order to get complete healing of the pathological condition, thus avoiding delay in the diagnosis.

Obturator Prosthesis Rehabilitation after Maxillectomy: Functional and Aesthetical Analysis in 25 Patients.

The number of patients undergoing a surgical resection of the maxilla for oncological reasons is constantly increasing, the most common complication of which remains the communication between oral and nasal cavities. On the basis of data arising from the literature regarding the treatment options of maxillary oncological post-surgical defects, obturator prosthesis remains the most used worldwide. We studied 25 patients (with at least 1-year follow up) rehabilitated by obturator prosthesis after maxillary resection leading to oro-nasal communication, providing data on the objective/subjective evaluation of such rehabilitation and mastication performance measured by a two-color chewing gum test. The type of defect was classified according to the classification system proposed by Aramany. Among the patients in our study, 72% rated a higher score for either stability and retention than for aesthetic appearance, as confirmed by the Kapur score rated by clinicians. The two-color chewing gum test shows similar results as only one patient had insufficient chewing function. Interestingly, we found no correlation between the masticatory function and residual denture, confirming that the maxillary obturator remains a predictable solution in such patients regardless of the anatomical alterations following surgery.

Oral and Maxillo-Facial Manifestations of Systemic Diseases: An Overview.

Many systemic (infective, genetic, autoimmune, neoplastic) diseases may involve the oral cavity and, more generally, the soft and hard tissues of the head and neck as primary or secondary localization. Primary onset in the oral cavity of both pediatric and adult diseases usually represents a true challenge for clinicians; their precocious detection is often difficult and requires a wide knowledge but surely results in the early diagnosis and therapy onset with an overall better prognosis and clinical outcomes. In the current paper, as for the topic of the current Special Issue, the authors present an overview on the most frequent clinical manifestations at the oral and maxillo-facial district of systemic disease.