{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:12:36Z","timestamp":1788351156495,"version":"build-2803163510"},"reference-count":177,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T00:00:00Z","timestamp":1661644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the University of Medicine and Pharmacy of Craiova, Romania","award":["VAT\/CIF: 10815397"],"award-info":[{"award-number":["VAT\/CIF: 10815397"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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\u2019s 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\u201380% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F \u00b1 IL-22, and probably a high mucosal concentration of interferon (IFN)-\u03b3. 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\u2019s disease also presents oral ulceration (OU), mucogingivitis, and a 2\u20133 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.<\/jats:p>","DOI":"10.3390\/diagnostics12092080","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T01:39:19Z","timestamp":1661737159000},"page":"2080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden"],"prefix":"10.3390","volume":"12","author":[{"given":"Narcis Mih\u0103i\u0163\u0103","family":"Bug\u0103l\u0103","sequence":"first","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"C.I. Parhon National Institute of Endocrinology, Aviatorilor Ave. 34\u201338, Sector 1, 011683 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana Elena","family":"Stoica","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana Maria","family":"Albulescu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6535-3152","authenticated-orcid":false,"given":"Mihaela Jana","family":"\u0162uculin\u0103","sequence":"additional","affiliation":[{"name":"Department of Odontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smaranda Adelina","family":"Preda","sequence":"additional","affiliation":[{"name":"Department of Odontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancuta-Ramona","family":"Boicea","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-8048","authenticated-orcid":false,"given":"Drago\u0219 Ovidiu","family":"Alexandru","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s12020-021-02649-6","article-title":"Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis","volume":"71","author":"Nowotny","year":"2021","journal-title":"Endocrine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(21)00136-7","article-title":"Adrenal insufficiency","volume":"397","author":"Husebye","year":"2021","journal-title":"Lancet"},{"key":"ref_3","first-page":"181","article-title":"Hyperpigmentation of the Tongue and Buccal Mucosa","volume":"102","author":"Rehman","year":"2020","journal-title":"Am. 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