Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

Perniola, Roberto; Fierabracci, Alessandra; Falorni, Alberto

doi:10.3389/fimmu.2021.606860

Cited by 21 publications

(19 citation statements)

References 315 publications

(235 reference statements)

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“…Even though the sequence of appearance of the classic features of APS1 is important in the clinical diagnosis of the syndrome, the appearance of AD as the first manifestation in our case was unexpectedly different from the conventional. This fact strengthens the idea that diagnosis of APS1 should be considered in all patients who present with 1 of the classic clinical manifestations [ 13 ].…”

Section: Discussionsupporting

confidence: 79%

Hypoadrenalism as the Single Presentation of Autoimmune Polyglandular Syndrome Type 1

Nasser

Samra

Naccache

2021

Journal of the Endocrine Society

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Type-1 autoimmune polyglandular syndrome (APS1) is a rare hereditary disease affecting nearly 600 patients worldwide. The first of its cardinal manifestations, chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HPT), or Addison’s disease (AD), presents in childhood. Additional non-classical landmarks of APS1 continue to develop as late as the fifth decade of life. Two-thirds of patients develop the full triad before 25 years of age. Only 20% of patients develop the entire triad simultaneously. Addison's disease is rarely reported as the first manifestation.According to APS1 classifications, restricted criteria for a single cardinal component, although elements of suspicion are not sufficient to diagnose APS1.This case report is peculiar as hypoadrenalism was the first and only manifestation of APS1 for nearly three decades since its diagnosis. Theoretically, exceptions from the protocol of APS1 diagnostic criteria would be recognized as acceptable for diagnosis in the future, when similar case reports of only one component of APS1 appear.

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Section: Discussionsupporting

confidence: 79%

Hypoadrenalism as the Single Presentation of Autoimmune Polyglandular Syndrome Type 1

Nasser

Samra

Naccache

2021

Journal of the Endocrine Society

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“…Trivially, polyglandular syndromes (PGS) type 1, 2, and 3 are highly associated ( Figure 2 ). PGS type 1 is an autosomal recessive syndrome due to mutation of the AIRE gene, resulting in hypoparathyroidism, adrenal insufficiency, hypogonadism, vitiligo, candidiasis, and others [ 52 ]. PGS type 2 combines Addison’s disease along with autoimmune thyroid disease and/or type 1 diabetes [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

“…Finally, PGS type 3 is the combination of autoimmune Hashimoto’s thyroiditis with another organ-specific autoimmune disease, such as diabetes mellitus, pernicious anemia, vitiligo, alopecia, myasthenia gravis, and Sjögren’s syndrome, as shown in Figure 3 . The distinction between these is blurred by their association with coinciding AIDs [ 52 ]. Notably, PGS are also known as autoimmune polyendocrine syndrome.…”

Section: Resultsmentioning

confidence: 99%

Autoimmune Disease Classification Based on PubMed Text Mining

Samuels

Malov

Saha

et al. 2022

JCM

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Autoimmune diseases (AIDs) are often co-associated, and about 25% of patients with one AID tend to develop other comorbid AIDs. Here, we employ the power of datamining to predict the comorbidity of AIDs based on their normalized co-citation in PubMed. First, we validate our technique in a test dataset using earlier-reported comorbidities of seven knowns AIDs. Notably, the prediction correlates well with comorbidity (R = 0.91) and validates our methodology. Then, we predict the association of 100 AIDs and classify them using principal component analysis. Our results are helpful in classifying AIDs into one of the following systems: (1) gastrointestinal, (2) neuronal, (3) eye, (4) cutaneous, (5) musculoskeletal, (6) kidneys and lungs, (7) cardiovascular, (8) hematopoietic, (9) endocrine, and (10) multiple. Our classification agrees with experimentally based taxonomy and ranks AID according to affected systems and gender. Some AIDs are unclassified and do not associate well with other AIDs. Interestingly, Alzheimer’s disease correlates well with other AIDs such as multiple sclerosis. Finally, our results generate a network classification of autoimmune diseases based on PubMed text mining and help map this medical universe. Our results are expected to assist healthcare workers in diagnosing comorbidity in patients with an autoimmune disease, and to help researchers in identifying common genetic, environmental, and autoimmune mechanisms.

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“…As mentioned, autoimmune hypoparathyroidism is the earliest endocrine dysfunction in APS1, and thus children might experience the dental complications of persistent low parathormone (PTH) and low calcium levels [ 74 , 75 , 76 ]. Short dental roots, a challenge for orthodontists, with or without enamel hypoplasia/dysplasia are mostly reported [ 74 , 75 , 77 ]. These may be identified before the actual diagnosis of autoimmune AD [ 74 , 75 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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.

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Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

Cited by 21 publications

References 315 publications

Hypoadrenalism as the Single Presentation of Autoimmune Polyglandular Syndrome Type 1

Hypoadrenalism as the Single Presentation of Autoimmune Polyglandular Syndrome Type 1

Autoimmune Disease Classification Based on PubMed Text Mining

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

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