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 colposcopy and histologic results from colposcopically directed biopsy in cervical precancerous lesions.

INTRODUCTION: Cervical cancer develops from well-defined precursor lesions in a varied period of time. Detected in early or pre-invasive stages, cervical cancer is preventable and curable, so detection of precancerous lesions is very important. Colposcopy with directed biopsy is used in the evaluation and management of patients with cervical lesions, and described as the 'gold standard' for the diagnosis of cervical precancer. AIM: The aim of this study is to assess the accuracy of colposcopic examination and cervical punch biopsy, to determine the correlation between these two methods. MATERIALS AND METHODS: We examined 245 patients who present malignant findings at colposcopy and biopsy. Colposcopic findings in our study group: 28 (11.4%) cases were CIN I, 50 (20.4%) cases were CIN II, 150 (61.2%) cases were CIN III, 13 (5.3%) cases were micro-invasive carcinoma and four (1.6%) cases were CIS. Histological results in the 245 examined cases were: four (1.6%) cases normal, 26 (10.6%) cases CIN I, 55 (22.4%) cases CIN II, 138 (56.3%) cases CIN III, 15 (6.1%) cases micro-invasive carcinoma and seven (2.8%) cases of CIS. RESULTS: The correlation was 78.5% in the CIN I category, 84% in the CIN II category, 88.6% (133 out of 150 patients) in the CIN III category, 46.1% for micro-invasive carcinoma and 50% for CIS. The colposcopy method incurred fewer false negatives (four patients), giving a general accuracy rate of 98.3%. Sensitivity of colposcopic examination was 83.6%. CONCLUSIONS: This study demonstrated high accuracy and correlation between colposcopy and histology, comparable with results from similar studies in the literature. Sensitivity is lower, probably because biopsies were done in all cases, during diagnostic work-up. We also demonstrated the usefulness of these two diagnostic procedures as screening tests in preclinical cervical cancer. In our study, there were cases of under or over diagnose; the benefit of colposcopy and directed biopsy is to avoid over treatment of low-grade lesion, and under treatment of high-grade lesion.