This review highlights oral anomalies with major clinical impact in Addison disease (AD), including dental health and dermatologic features, through a dual perspective: pigmentation issues and AD comorbidities with oral manifestations. Affecting 92% of AD patients, cutaneomucosal hyperpigmentation is synchronous with or precedes general manifestations by up to a decade, underlying melanocytic infiltration of the basal epidermal layer; melanophages in the superficial dermis; and, rarely, acanthosis, perivascular lymphocytic infiltrate, and hyperkeratosis. Intraoral pigmentation might be the only sign of AD; thus, early recognition is mandatory, and biopsy is helpful in selected cases. The buccal area is the most affected location; other sites are palatine arches, lips, gums, and tongue. Pigmented oral lesions are patchy or diffuse; mostly asymptomatic; and occasionally accompanied by pain, itchiness, and burn-like lesions. Pigmented lingual patches are isolated or multiple, located on dorsal and lateral areas; fungiform pigmented papillae are also reported in AD individuals. Dermoscopy examination is particularly indicated for fungal etiology; yet, it is not routinely performed. AD’s comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction. Chronic cutaneomucosal candidiasis (CMC), including oral CMC, represents the first sign of APS1 in 70–80% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F ± IL-22, and probably a high mucosal concentration of interferon (IFN)-γ. CMC is prone to systemic candidiasis, representing a procarcinogenic status due to Th17 cell anomalies. In APS1, the first cause of mortality is infections (24%), followed by oral and esophageal cancers (15%). Autoimmune hypoparathyroidism (HyP) is the earliest endocrine element in APS1; a combination of CMC by the age of 5 years and dental enamel hypoplasia (the most frequent dental complication of pediatric HyP) by the age of 15 is an indication for HyP assessment. Children with HyP might experience short dental roots, enamel opacities, hypodontia, and eruption dysfunctions. Copresence of APS-related type 1 diabetes mellitus (DM) enhances the risk of CMC, as well as periodontal disease (PD). Anemia-related mucosal pallor is related to DM, hypothyroidism, hypogonadism, corresponding gastroenterological diseases (Crohn’s disease also presents oral ulceration (OU), mucogingivitis, and a 2–3 times higher risk of PD; Biermer anemia might cause hyperpigmentation by itself), and rheumatologic diseases (lupus induces OU, honeycomb plaques, keratotic plaques, angular cheilitis, buccal petechial lesions, and PD). In more than half of the patients, associated vitiligo involves depigmentation of oral mucosa at different levels (palatal, gingival, alveolar, buccal mucosa, and lips). Celiac disease may manifest xerostomia, dry lips, OU, sialadenitis, recurrent aphthous stomatitis and dental enamel defects in children, a higher prevalence of caries and dentin sensitivity, and gingival bleeding. Oral pigmented lesions might provide a useful index of suspicion for AD in apparently healthy individuals, and thus an adrenocorticotropic hormone (ACTH) stimulation is useful. The spectrum of autoimmune AD comorbidities massively complicates the overall picture of oral manifestations.

/pdf/new-approach-to-addison-disease-oral-manifestations-due-to-7c166jw0.pdf

New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden

Matrix metalloproteinases (MMPs) are a large family of Ca2+ and Zn2+ dependent proteolytic enzymes, able to cleave the various components of the extracellular matrix (ECM), as well as a range of other regulatory molecules. Several reports have proven the important role of both MMPs and their endogenous inhibitors, TIPMs, in oral health, the initial development of the tooth, and during enamel maturation. In this mini-review, we aim to summarize the literature information about the functions of MMPs, paying more attention to MMP-8 (collagenase-2 or neutrophil collagenase) in the development and progression of periodontitis, peri-implantitis, and carious lesions. We also emphasize the role of particular gene variants in MMP8 as predisposing factors for some oral diseases.

https://www.mdpi.com/2227-9059/11/6/1514/pdf?version=1685084047

Matrix Metalloproteinases in Oral Health—Special Attention on MMP-8

Introduction When collected in a standardized fashion, oral fluid analysis can refine the diagnosis of periodontal and peri-implant disease. In practice, dental professionals can perform active matrix metalloproteinase (aMMP-8) analysis chairside. 

aMMP-8 point-of-care - diagnostic methods and treatment modalities in periodontitis and peri-implantitis

Abstract Objective  The complete removal of bacterial plaque and their endotoxins in deeper areas of periodontal pockets is often difficult to achieve with conventional methods such as periodontal pocket curettage. An alternative to these methods that recently gained popularity in periodontology is the diode laser, with its antibacterial effect, angiogenesis promotion as advantages. Materials and Methods  This study included 100 patients diagnosed with chronic periodontitis, with periodontal pockets up to 6 mm, and who were divided into two groups: patients treated with basic therapy and diode laser application, and patients treated with basic therapy and with flap surgery. The clinical periodontal evaluation was done before the treatment and 6 months after the treatment. Evaluation of matrix metalloproteinase (MMP)-8 as an inflammatory indicator in gingival exudate was done with dipstick immunoassay test before the treatment and 6 months later. Results  This study showed a more pronounced improvement of periodontal clinical parameters, as well as a decrease in MMP-8 values in gingival exudate in the laser-treated group compared with the surgically treated group. Conclusion  The results of this study are encouraging for the use of the diode laser as a noninvasive method in the treatment of periodontal pathologies.

/pdf/the-effect-of-periodontal-therapy-on-the-level-of-mmp-8-in-1dhwlrxw.pdf

The Effect of Periodontal Therapy on the Level of MMP-8 in Patients with Chronic Periodontitis

Early and minimally invasive methods are required to predict the risk of multiple adverse pregnancy outcomes. A potential technique with growing interest utilizes the gingival crevicular fluid (GCF), a physiological serum exudate found in the healthy gingival sulcus and in the periodontal pocket in inflammatory conditions. Analysis of biomarkers in the GCF is a minimally invasive method that can be feasible and cost-effective. The potential use of GCF biomarkers along with other clinical indicators in early pregnancy may provide reliable predictors of several adverse pregnancy outcomes, therefore, reducing both maternal and fetal morbidities. Various studies have reported that increased or decreased concentrations of different biomarkers in GCF are associated with a high risk of developing pregnancy complications. In particular, such associations have been commonly demonstrated with gestational diabetes, pre-eclampsia, and pre-term birth. However, limited evidence is available regarding other pregnancy complications such as preterm premature rupture of membranes, recurrent miscarriage, small for gestational age, and hyperemesis gravidarum. In this review, we discuss the reported association between individual GCF biomarkers and common pregnancy complications. Future research is required to provide more solid evidence of the predictive value of those biomarkers in estimating women’s risk for each disorder.

/pdf/the-potential-role-of-the-gingival-crevicular-fluid-3i9aa3su.pdf

The potential role of the gingival crevicular fluid biomarkers in the prediction of pregnancy complications

Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases.

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Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases.