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

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.

Correlations between periodontal indices and osteoporosis.

In the pathogenesis of chronic periodontitis, there are general systemic factors which play a major role, such as osteoporosis, with menopause as the most common etiological factor, and other pathological determining conditions for osteoporosis as well (ovary, thyroid and malignant tumors). The aim of the present study was to assess the correlations between periodontal indices and osteoporosis. The study was performed on 35 patients with periodontal disease aged between 45 and 79 years. These patients were divided into two groups: a study group with osteoporosis and periodontal disease (n=25) and a control group with periodontal disease (n=10) only. The periodontal assessment included community periodontal index (CPI), gingival inflammation index (GI), plaque index (PI), body mass index (BMI), bone mineral density (BMD), tooth mobility and tooth loss. Osteoporosis was assessed by dual-energy X-ray absorptiometry. Results were statistically analyzed with Microsoft Excel software and XLSTAT. The results showed that patients in the study group had higher values of periodontal indices, and a highly significant inverse correlation was observed between the CPI and the tooth loss. Inverse correlations between BMI and tooth mobility, as well as BMI and CPI were determined for the study group. In conclusion, the positive association between BMD and GI shows that the gingival index can be a predictive factor in the occurrence of osteoporosis.

Histopathological and immunohistochemical changes of the marginal periodontium in patients with Turner syndrome.

Turner syndrome (TS) is characterized by partial or complete loss of a sexual chromosome, resulting in an incomplete development of the body, gonadic failure, cardiac and renal abnormalities, oro-dental changes, etc. In our study, we proposed to perform a histological and immunohistochemical (IHC) study of the periodontium changes in patients with TS. The biological material under study was represented by fragments of gingival mucosa harvested from 18 patients with TS who presented advanced periodontal lesions and required dental extractions. The fragments of gingival mucosa were processed by the classical histological technique of paraffin inclusion, subsequently the obtained sections being stained by the Hematoxylin-Eosin (HE) and examined under the optical microscope. For the IHC study, there were performed serial sections incubated with anti-cluster of differentiation (CD) 3, anti-CD20 and anti-CD68 antibodies for highlighting immune cells, as well as with anti-matrix metalloproteinase (MMP) 2 and anti-MMP8 antibodies for highlighting MMPs (MMP2 and MMP8) involved in the periodontal tissue lesions. In the present study, during the histological examination, there were observed morphological changes, both in the epithelium and in the gingival mucosa chorion. Epithelial changes consisted in the onset of acanthosis processes, in the thickening of the epithelium due to the increase of the spinous layer, as well as in the parakeratosis phenomenon. In the chorion, there was observed the presence of inflammatory infiltrates in various stages, presence of fibrosis (extended in some cases) and the presence of an important vascularization in some cases, with a high number of immunocompetent cells involved in the inborn immune response, but also in the adaptive one, as well as a more or less intense immunoexpression of MMP2 and MMP8. Our study suggests that TS may contribute to the development of some inflammatory processes in the marginal periodontium.

Craniofacial morphology aspects in children with isolated growth hormone deficiency - a cephalometric study.

Craniofacial and dental morphology is influenced by different circulating hormones, but it is of particular importance that there is growth hormone (GH) in normal craniofacial and teeth development. Craniofacial morphometry studies in children with GH deficiency show different changes in certain anthropometric variables in the sense of reducing their values compared to normal children's developmental norms in different stages of childhood and adolescence. Therefore, the early establishment of GH replacement therapy can correct craniofacial morphological changes induced by GH deficiency. In our study, we evaluated different anthropometric craniofacial variables at children with GH deficiency and we established some anthropometric and morphological characteristics associated with this pathology.