Autoimmune polyendocrine syndrome differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Overview

Autoimmune polyendocrine syndrome (APS) must be differentiated from other similar conditions which lead to multiple endocrine disorders such as thymoma, Kearns–Sayre syndrome, POEMS syndrome, and Wolfram syndrome. APS should also be differentiated among its subtypes such as APS type 1, type 2 and type 3.

Differentiating Autoimmune Polyendocrine Syndrome From Other Diseases

Different types of autoimmune polyendocrine syndrome should be differentiated from each other. The following table characterizes the differences among various sub-types of APS.[1][2][3][4][5][6][7]

Characterstic Autoimmune
polyendocrine syndrome
type 1
Autoimmune
polyendocrine syndrome
type 2
Autoimmune
polyendocrine syndrome
type 3
Inheritance Autosomal recessive Autosomal dominant X-linked
Gene(s) involved AIRE (transcription factor) Polygenic FOXP3 (transcription factor)
HLA genotype HLA-D3 and HLA-D4 HLA-DQ2 and HLA-DQ8; HLA-DRB1*0404 None
Pathogenesis Autoreactive T cells escape
negative selection
Unknown

Defective T cell regulation leading to T cell
activation and proliferation

Age of onset Infancy Infancy and adulthood Neonatal
Clinical features
(most common)

Candidiasis
Hypoparathyroidism
Addison’s disease

Addison’s disease
Diabetes mellitus type 1A
Autoimmune thyroiditis

Autoimmune thyroiditis
Neonatal diabetes
Malabsorption

Diabetes 18% 20-50% >60%
Other manifestations
Hepatitis, malabsorption, asplenism,
oophoritis, alopecia and vitiligo
Autoimmune gastritis, celiac disease,
oophoritis and vitiligo
Autoimmune thyroiditis, haemolytic anemia,
thrombocytopenia and lymphadenopathy
Gender predisposition Equal in males and females Females>males Males (X-linked)
Immunodeficiency Immunodeficienct No defined immunodeficiency Immunodeficient
Prevalence Rare Common Very rare

Autoimmune polyendocrine syndrome (APS) must be differentiated from other similar conditions which lead to multiple endocrine disorders such as POEMS syndrome, Hirata syndrome, Kearns–Sayre syndrome and Wolfram syndromes.[8][9][10][11][12]

Disease Addison's disease Type 1 diabetes mellitus Hypothyroidism Other disorders present
APS type 1 + Less common Less common Hypoparathyroidism
Candidiasis
Hypogonadism
APS type 2 + + + Hypogonadism
Malabsorption
APS type 3 - + + Malabsorption
Thymoma + - + Myasthenia gravis
Cushing syndrome
Chromosomal abnormalities
(Turner syndrome,
Down's syndrome)
- + + Cardiac dysfunction
Kearns–Sayre syndrome - + - Myopathy
Hypoparathyroidism
Hypogonadism
Wolfram syndrome - + - Diabetes insipidus
Optic atrophy
Deafness
POEMS syndrome - + - Polyneuropathy
Hypogonadism
Plasma cell dyscrasias

References

  1. Alimohammadi M, Björklund P, Hallgren A, Pöntynen N, Szinnai G, Shikama N, Keller MP, Ekwall O, Kinkel SA, Husebye ES, Gustafsson J, Rorsman F, Peltonen L, Betterle C, Perheentupa J, Akerström G, Westin G, Scott HS, Holländer GA, Kämpe O (2008). "Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen". N. Engl. J. Med. 358 (10): 1018–28. doi:10.1056/NEJMoa0706487. PMID 18322283.
  2. Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, Cobat A, Ouachée-Chardin M, Toulon A, Bustamante J, Al-Muhsen S, Al-Owain M, Arkwright PD, Costigan C, McConnell V, Cant AJ, Abinun M, Polak M, Bougnères PF, Kumararatne D, Marodi L, Nahum A, Roifman C, Blanche S, Fischer A, Bodemer C, Abel L, Lilic D, Casanova JL (2010). "Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I". J. Exp. Med. 207 (2): 291–7. doi:10.1084/jem.20091983. PMC 2822614. PMID 20123958.
  3. Alimohammadi, Mohammad; Björklund, Peyman; Hallgren, Åsa; Pöntynen, Nora; Szinnai, Gabor; Shikama, Noriko; Keller, Marcel P.; Ekwall, Olov; Kinkel, Sarah A.; Husebye, Eystein S.; Gustafsson, Jan; Rorsman, Fredrik; Peltonen, Leena; Betterle, Corrado; Perheentupa, Jaakko; Åkerström, Göran; Westin, Gunnar; Scott, Hamish S.; Holländer, Georg A.; Kämpe, Olle (2008). "Autoimmune Polyendocrine Syndrome Type 1 and NALP5, a Parathyroid Autoantigen". New England Journal of Medicine. 358 (10): 1018–1028. doi:10.1056/NEJMoa0706487. ISSN 0028-4793.
  4. Kisand K, Lilic D, Casanova JL, Peterson P, Meager A, Willcox N (2011). "Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications". Eur. J. Immunol. 41 (6): 1517–27. doi:10.1002/eji.201041253. PMID 21574164.
  5. Bacchetta R, Passerini L, Gambineri E, Dai M, Allan SE, Perroni L, Dagna-Bricarelli F, Sartirana C, Matthes-Martin S, Lawitschka A, Azzari C, Ziegler SF, Levings MK, Roncarolo MG (2006). "Defective regulatory and effector T cell functions in patients with FOXP3 mutations". J. Clin. Invest. 116 (6): 1713–22. doi:10.1172/JCI25112. PMC 1472239. PMID 16741580.
  6. Powell BR, Buist NR, Stenzel P (1982). "An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy". J. Pediatr. 100 (5): 731–7. PMID 7040622.
  7. Moraes-Vasconcelos D, Costa-Carvalho BT, Torgerson TR, Ochs HD (2008). "Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED". J. Clin. Immunol. 28 Suppl 1: S11–9. doi:10.1007/s10875-008-9176-5. PMID 18264745.
  8. Sherer Y, Bardayan Y, Shoenfeld Y (1997). "Thymoma, thymic hyperplasia, thymectomy and autoimmune diseases (Review)". Int. J. Oncol. 10 (5): 939–43. PMID 21533467.
  9. Nozza, Andrea (2017). "POEMS SYNDROME: AN UPDATE". Mediterranean Journal of Hematology and Infectious Diseases. 9 (1): e2017051. doi:10.4084/mjhid.2017.051. ISSN 2035-3006.
  10. Maceluch JA, Niedziela M (2006). "The clinical diagnosis and molecular genetics of kearns-sayre syndrome: a complex mitochondrial encephalomyopathy". Pediatr Endocrinol Rev. 4 (2): 117–37. PMID 17342029.
  11. Rigoli L, Di Bella C (2012). "Wolfram syndrome 1 and Wolfram syndrome 2". Curr. Opin. Pediatr. 24 (4): 512–7. doi:10.1097/MOP.0b013e328354ccdf. PMID 22790102.
  12. Husebye, Eystein S.; Anderson, Mark S. (2010). "Autoimmune Polyendocrine Syndromes: Clues to Type 1 Diabetes Pathogenesis". Immunity. 32 (4): 479–487. doi:10.1016/j.immuni.2010.03.016. ISSN 1074-7613.

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