Citation Information :
Goyal T, Yangdol P, Sabherwal P. A Rare Case of Autoimmune Polyendocrinopathy- candidiasis-ectodermal Dystrophy Syndrome: Dental Perspective on Diagnosis and Management. Int J Clin Pediatr Dent 2023; 16 (1):139-146.
Aim: To report a unique case of Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a young boy and discuss the oral health impact and management of the disease.
Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder with various clinical manifestations. Biallelic mutations in the autoimmune regulator (AIRE) gene lead to impairment of central immune tolerance and a targeted attack on various endocrine and non-endocrine organs. Patients classically suffer from a triad of disorders, including chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenocortical failure (Addison's disease).
Results: In recent times, it has been observed that oral manifestations of the disorder, such as enamel hypoplasia, appear early and frequently. Affected individuals require a comprehensive preventive and minimally invasive approach for oral health along with follow-up throughout their lifespan to manage potentially life-threatening disease manifestations.
Conclusion: Prompt recognition by a pediatric dentist can facilitate an earlier diagnosis and allow for screening, preventive and therapeutic services.
Clinical Significance: To deliver oral health care in an effective and comprehensive manner, clinicians should be able to recognize, diagnose and manage the signs and symptoms of the disease.
Dittmar M, Kahaly GJ. Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up. J Clin Endocrinol Metab 2003;88(7):2983–2992. DOI: 10.1210/jc.2002-021845
Neufeld MB, Blizzard RM. Polyglandular autoimmune diseases. In: Pinchera A, Doniach D, Fenzi GF, Baschieri L, eds. Symposium on autoimmune aspects of endocrine disorders. New York: Academic Press; 1980. pp. 357–365.
De Martino L, Capalbo D, Improda N, et al. APECED: a paradigm of complex interactions between genetic background and susceptibility factors. Front Immunol 2013;4:331. DOI: 10.3389/fimmu.2013.00331
Anderson MS, Venanzi ES, Chen Z, et al. The cellular mechanism of AIRE control of T cell tolerance. Immunity 2005;23(2):227–239. DOI: 10.1016/j.immuni.2005.07.005
Oftedal BE, Hellesen A, Erichsen MM, et al. Dominant mutations in the autoimmune regulator AIRE are associated with common organ-specific autoimmune diseases. Immunity 2015;42(6):1185–1196. DOI: 10.1016/j.immuni.2015.04.021
Ferre EM, Rose SR, Rosenzweig SD, et al. Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. JCI Insight 2016;1(13):e88782. DOI: 10.1172/jci.insight.88782
Brenchley L, Ferré EMN, Schmitt MM, et al. Case report: dental findings can aid in early diagnosis of APECED syndrome. Front Dent Med 2021;2:670624. DOI: 10.3389/fdmed.2021.670624
Zaidi G, Bhatia V, Sahoo SK, et al. Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study. Endocr Connect 2017;6(5):289–296. DOI: 10.1530/EC-17-0022
Fierabracci A, Arena A, Toto F, et al. Autoimmune polyendocrine syndrome type 1 (APECED) in the Indian population: case report and review of a series of 45 patients. J Endocrinol Invest 2021;44(4):661–677. DOI: 10.1007/s40618-020-01376-5
Greenberg MS, Brightman VJ, Lynch MA, et al. Idiopathic hypoparathyroidism, chronic candidiasis, and dental hypoplasia. Oral Surg Oral Med Oral Pathol 1969;28(1):42–53. DOI: 10.1016/0030-4220(69)90192-3
Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults. J Endocrinol Invest 2019;42(12):1407–1433. DOI: 10.1007/s40618-019-01079-6
Meloni A, Furcas M, Cetani F, et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 2008;93(11):4389–4397. DOI: 10.1210/jc.2008-0935
Graham A, Javidi H, Stern M, et al. The impacts of autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia (APECED) on the oral health of children and young people: a review and case report. J Adv Oral Res 2022;13(1):29–37. DOI: 10.1177/23202068221075961
Weiler FG, Dias-da-Silva MR, Lazaretti-Castro M. Autoimmune polyendocrine syndrome type 1: case report and review of literature. Arq Bras Endocrinol Metabol 2012;56(1):54–66. DOI: 10.1590/s0004-27302012000100009
Ferré EMN, Schmitt MM, Lionakis MS. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Front Pediatr 2021;9:723532. DOI: 10.3389/fped.2021.723532
Winer KK, Ye S, Ferré EMN, et al. Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center. Bone 2021;149:115977. DOI: 10.1016/j.bone.2021.115977
Winer KK, Kelly A, Johns A, et al. Long-term parathyroid hormone 1-34 replacement therapy in children with hypoparathyroidism. J Pediatr 2018;203:391–399. DOI: 10.1016/j.jpeds.2018.08.010
Saari V, Holopainen E, Makitie O, et al. Pubertal development and premature ovarian insufficiency in patients with APECED. Eur J Endocrinol 2020;183(5):513–520. DOI: 10.1530/EJE-20-0516
Rautemaa R, Hietanen J, Niissalo S, et al. Oral and oesophageal squamous cell carcinoma–a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I). Oral Oncol 2007;43(6):607–613. DOI: 10.1016/j.oraloncology.2006.07.005
Rautemaa R, Richardson M, Pfaller M, et al. Reduction of fluconazole susceptibility of Candida albicans in APECED patients due to long-term use of ketoconazole and miconazole. Scand J Infect Dis 2008;40(11-12):904–907. DOI: 10.1080/00365540802275853
McManus BA, McGovern E, Moran GP, et al. Microbiological screening of Irish patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy reveals persistence of Candida albicans strains, gradual reduction in susceptibility to azoles, and incidences of clinical signs of oral candidiasis without culture evidence. J Clin Microbiol 2011;49(5):1879–1889. DOI: 10.1128/JCM.00026-11
McGovern E, Fleming P, Costigan C, et al. Oral health in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). Eur Arch Paediatr Dent 2008;9(4):236–244. DOI: 10.1007/BF03262642
Lukinmaa PL, Waltimo J, Pirinen S. Microanatomy of the dental enamel in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED): report of three cases. J Craniofac Genet Dev Biol 1996;16(3):174–181.
Perniola R, Tamborrino G, Marsigliante S, et al. Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Oral Pathol Med 1998;27(6):278–282. DOI: 10.1111/j.1600-0714.1998.tb01956.x
Ahonen P, Myllarniemi S, Sipila I, et al. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. New Engl J Med 1990;322(26):1829–1836. DOI: 10.1056/NEJM199006283222601
Elshimy G, Chippa V, Jeong JM. Adrenal Crisis. [Updated 2022 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499968/
Khadilkar V, Lohiya N, Chiplonkar S, et al. Body mass index quick screening tool for Indian academy of pediatrics 2015 growth charts. Indian Pediatr 2020;57(10):904–906.
Malamed SF. Medical emergencies in the dental office e-book. Elsevier Health Sciences; 2022 Jan 31.
Crystal YO, Janal MN, Yim S, et al. Teaching and utilization of silver diamine fluoride and Hall-style crowns in US pediatric dentistry residency programs. J Am Dent Assoc 2020;151(10):755–763. DOI: 10.1016/j.adaj.2020.06.022
Indrapriyadharshini K, Madan Kumar PD, Sharma K, et al. Remineralizing potential of CPP-ACP in white spot lesions - A systematic review. Indian J Dent Res 2018;29(4):487–496. DOI: 10.4103/ijdr.IJDR_364_17
Bruserud Ø, Siddiqui H, Marthinussen MC, et al. Oral microbiota in autoimmune polyendocrine syndrome type 1. J Oral Microbiol 2018;10(1):1442986. DOI: 10.1080/20002297.2018.1442986
Pavlic A, Waltimo-Sirén J. Clinical and microstructural aberrations of enamel of deciduous and permanent teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Arch Oral Biol 2009;54(7):658–665. DOI: 10.1016/j.archoralbio.2009.03.009
